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Digestive Disease Interventions 2021; 05(01): 032-049
DOI: 10.1055/s-0040-1721799
Review Article

Cancer Immunology and Immuno-Oncology (Innate vs. Adaptive Cell Immunity)

Nariman Nezami
1   Division of Interventional Radiology and Image-Guided Medicine, Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, Georgia
,
Carlos J. Sanchez
1   Division of Interventional Radiology and Image-Guided Medicine, Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, Georgia
,
John Moon
1   Division of Interventional Radiology and Image-Guided Medicine, Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, Georgia
,
Jamil Shaikh
1   Division of Interventional Radiology and Image-Guided Medicine, Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, Georgia
,
Nima Kokabi
1   Division of Interventional Radiology and Image-Guided Medicine, Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, Georgia
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Abstract

Tumorigenesis occurs due to both intrinsic cellular genetic changes and imbalances within the tumor microenvironment. This microenvironment is composed of a complex ecosystem of tumor cells, vasculature, extracellular matrix, stromal cells, and immune cells. With these cells, there is both immune activation and immune suppression that promote or inhibit tumor development. These interactions lead to a constant flux of remodeling within the tumor microenvironment that additionally promote or inhibits tumor metastasis. To promote or suppress either antitumorigenic or protumorigenic effects, it is important to understand the complex interactions of the tumor and its interactions with the immune system within the tumor microenvironment. This review article addresses the role of the immune system and its cellular components within the tumor microenvironment.

Keywords

tumor - innate - adaptive - immune - lymphocyte - macrophage - dendritic cell - natural killer cell


Publikationsverlauf

Eingereicht: 02. September 2020

Angenommen: 22. Oktober 2020

Artikel online veröffentlicht:
31. Dezember 2020

© 2020. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

  • References

  • 1 Pardoll D. Cancer and the immune system: basic concepts and targets for intervention. Semin Oncol 2015; 42 (04) 523-538
    CrossrefPubMedGoogle Scholar
  • 2 van der Burg SH, Marincola F. Editorial overview: tumour immunology: What's beyond today's success in tumor immunology. Curr Opin Immunol 2016; 39: viii-x
    CrossrefPubMedGoogle Scholar
  • 3 Weiner LM. Cancer immunology for the clinician. Clin Adv Hematol Oncol 2015; 13 (05) 299-306
    PubMedGoogle Scholar
  • 4 Ventola CL. Cancer immunotherapy, Part 1: Current strategies and agents. P&T 2017; 42 (06) 375-383
    PubMedGoogle Scholar
  • 5 Klener Jr P, Otáhal P, Lateckova L, Klener P. Immunotherapy approaches in cancer treatment. Curr Pharm Biotechnol 2015; 16 (09) 771-781
    CrossrefPubMedGoogle Scholar
  • 6 Zugazagoitia J, Guedes C, Ponce S, Ferrer I, Molina-Pinelo S, Paz-Ares L. Current challenges in cancer treatment. Clin Ther 2016; 38 (07) 1551-1566
    CrossrefPubMedGoogle Scholar
  • 7 Chiriva-Internati M, Bot A. A new era in cancer immunotherapy: discovering novel targets and reprogramming the immune system. Int Rev Immunol 2015; 34 (02) 101-103
    CrossrefPubMedGoogle Scholar
  • 8 Yang Y. Cancer immunotherapy: harnessing the immune system to battle cancer. J Clin Invest 2015; 125 (09) 3335-3337
    CrossrefPubMedGoogle Scholar
  • 9 Quail DF, Joyce JA. Microenvironmental regulation of tumor progression and metastasis. Nat Med 2013; 19 (11) 1423-1437
    CrossrefPubMedGoogle Scholar
  • 10 Wang M, Zhao J, Zhang L. et al. Role of tumor microenvironment in tumorigenesis. J Cancer 2017; 8 (05) 761-773
    CrossrefPubMedGoogle Scholar
  • 11 Gajewski TF, Schreiber H, Fu YX. Innate and adaptive immune cells in the tumor microenvironment. Nat Immunol 2013; 14 (10) 1014-1022
    CrossrefPubMedGoogle Scholar
  • 12 Chang RB, Beatty GL. The interplay between innate and adaptive immunity in cancer shapes the productivity of cancer immunosurveillance. J Leukoc Biol 2020; 108 (01) 363-376
    CrossrefPubMedGoogle Scholar
  • 13 Bonasio R, von Andrian UH. Generation, migration and function of circulating dendritic cells. Curr Opin Immunol 2006; 18 (04) 503-511
    CrossrefPubMedGoogle Scholar
  • 14 Riboldi E, Musso T, Moroni E. et al. Cutting edge: proangiogenic properties of alternatively activated dendritic cells. J Immunol 2005; 175 (05) 2788-2792
    CrossrefPubMedGoogle Scholar
  • 15 Benencia F, Sprague L, McGinty J, Pate M, Muccioli M. Dendritic cells the tumor microenvironment and the challenges for an effective antitumor vaccination. J Biomed Biotechnol 2012; 2012: 425476
    CrossrefPubMedGoogle Scholar
  • 16 León B, Ardavín C. Monocyte-derived dendritic cells in innate and adaptive immunity. Immunol Cell Biol 2008; 86 (04) 320-324
    CrossrefPubMedGoogle Scholar
  • 17 Gardner A, Ruffell B. Dendritic cells and cancer immunity. Trends Immunol 2016; 37 (12) 855-865
    CrossrefPubMedGoogle Scholar
  • 18 Haniffa M, Shin A, Bigley V. et al. Human tissues contain CD141hi cross-presenting dendritic cells with functional homology to mouse CD103+ nonlymphoid dendritic cells. Immunity 2012; 37 (01) 60-73
    CrossrefPubMedGoogle Scholar
  • 19 Zilionis R, Engblom C, Pfirschke C. et al. Single-cell transcriptomics of human and mouse lung cancers reveals conserved myeloid populations across individuals and species. Immunity 2019; 50 (05) 1317-1334.e10
    CrossrefPubMedGoogle Scholar
  • 20 Veglia F, Gabrilovich DI. Dendritic cells in cancer: the role revisited. Curr Opin Immunol 2017; 45: 43-51
    CrossrefPubMedGoogle Scholar
  • 21 Guilliams M, Ginhoux F, Jakubzick C. et al. Dendritic cells, monocytes and macrophages: a unified nomenclature based on ontogeny. Nat Rev Immunol 2014; 14 (08) 571-578
    CrossrefPubMedGoogle Scholar
  • 22 Roberts EW, Broz ML, Binnewies M. et al. Critical role for CD103(+)/CD141(+) dendritic cells bearing CCR7 for tumor antigen trafficking and priming of T cell immunity in melanoma. Cancer Cell 2016; 30 (02) 324-336
    CrossrefPubMedGoogle Scholar
  • 23 Diamond MS, Kinder M, Matsushita H. et al. Type I interferon is selectively required by dendritic cells for immune rejection of tumors. J Exp Med 2011; 208 (10) 1989-2003
    CrossrefPubMedGoogle Scholar
  • 24 Sittig SP, Bakdash G, Weiden J. et al. A comparative study of the T cell stimulatory and polarizing capacity of human primary blood dendritic cell subsets. Mediators Inflamm 2016; 2016: 3605643
    CrossrefPubMedGoogle Scholar
  • 25 Janssen EM, Lemmens EE, Wolfe T, Christen U, von Herrath MG, Schoenberger SP. CD4+ T cells are required for secondary expansion and memory in CD8+ T lymphocytes. Nature 2003; 421 (6925): 852-856
    CrossrefPubMedGoogle Scholar
  • 26 Shedlock DJ, Shen H. Requirement for CD4 T cell help in generating functional CD8 T cell memory. Science 2003; 300 (5617): 337-339
    CrossrefPubMedGoogle Scholar
  • 27 Treilleux I, Blay JY, Bendriss-Vermare N. et al. Dendritic cell infiltration and prognosis of early stage breast cancer. Clin Cancer Res 2004; 10 (22) 7466-7474
    CrossrefPubMedGoogle Scholar
  • 28 Zou W, Machelon V, Coulomb-L'Hermin A. et al. Stromal-derived factor-1 in human tumors recruits and alters the function of plasmacytoid precursor dendritic cells. Nat Med 2001; 7 (12) 1339-1346
    CrossrefPubMedGoogle Scholar
  • 29 Shi C, Pamer EG. Monocyte recruitment during infection and inflammation. Nat Rev Immunol 2011; 11 (11) 762-774
    CrossrefPubMedGoogle Scholar
  • 30 Qian BZ, Li J, Zhang H. et al. CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis. Nature 2011; 475 (7355): 222-225
    CrossrefPubMedGoogle Scholar
  • 31 Hanna RN, Cekic C, Sag D. et al. Patrolling monocytes control tumor metastasis to the lung. Science 2015; 350 (6263): 985-990
    CrossrefPubMedGoogle Scholar
  • 32 Engblom C, Pfirschke C, Pittet MJ. The role of myeloid cells in cancer therapies. Nat Rev Cancer 2016; 16 (07) 447-462
    CrossrefPubMedGoogle Scholar
  • 33 Ziegler-Heitbrock L, Ancuta P, Crowe S. et al. Nomenclature of monocytes and dendritic cells in blood. Blood 2010; 116 (16) e74-e80
    CrossrefPubMedGoogle Scholar
  • 34 Yona S, Kim KW, Wolf Y. et al. Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis. Immunity 2013; 38 (01) 79-91
    CrossrefPubMedGoogle Scholar
  • 35 Franklin RA, Liao W, Sarkar A. et al. The cellular and molecular origin of tumor-associated macrophages. Science 2014; 344 (6186): 921-925
    CrossrefPubMedGoogle Scholar
  • 36 Movahedi K, Laoui D, Gysemans C. et al. Different tumor microenvironments contain functionally distinct subsets of macrophages derived from Ly6C(high) monocytes. Cancer Res 2010; 70 (14) 5728-5739
    CrossrefPubMedGoogle Scholar
  • 37 Broz ML, Binnewies M, Boldajipour B. et al. Dissecting the tumor myeloid compartment reveals rare activating antigen-presenting cells critical for T cell immunity. Cancer Cell 2014; 26 (06) 938
    CrossrefPubMedGoogle Scholar
  • 38 Veglia F, Perego M, Gabrilovich D. Myeloid-derived suppressor cells coming of age. Nat Immunol 2018; 19 (02) 108-119
    CrossrefPubMedGoogle Scholar
  • 39 Mitchem JB, Brennan DJ, Knolhoff BL. et al. Targeting tumor-infiltrating macrophages decreases tumor-initiating cells, relieves immunosuppression, and improves chemotherapeutic responses. Cancer Res 2013; 73 (03) 1128-1141
    CrossrefPubMedGoogle Scholar
  • 40 Li X, Yao W, Yuan Y. et al. Targeting of tumour-infiltrating macrophages via CCL2/CCR2 signalling as a therapeutic strategy against hepatocellular carcinoma. Gut 2017; 66 (01) 157-167
    CrossrefPubMedGoogle Scholar
  • 41 Tiemessen MM, Jagger AL, Evans HG, van Herwijnen MJ, John S, Taams LS. CD4+CD25+Foxp3+ regulatory T cells induce alternative activation of human monocytes/macrophages. Proc Natl Acad Sci U S A 2007; 104 (49) 19446-19451
    CrossrefPubMedGoogle Scholar
  • 42 De Palma M, Venneri MA, Galli R. et al. Tie2 identifies a hematopoietic lineage of proangiogenic monocytes required for tumor vessel formation and a mesenchymal population of pericyte progenitors. Cancer Cell 2005; 8 (03) 211-226
    CrossrefPubMedGoogle Scholar
  • 43 Coffelt SB, Tal AO, Scholz A. et al. Angiopoietin-2 regulates gene expression in TIE2-expressing monocytes and augments their inherent proangiogenic functions. Cancer Res 2010; 70 (13) 5270-5280
    CrossrefPubMedGoogle Scholar
  • 44 Gordon IO, Freedman RS. Defective antitumor function of monocyte-derived macrophages from epithelial ovarian cancer patients. Clin Cancer Res 2006; 12 (05) 1515-1524
    CrossrefPubMedGoogle Scholar
  • 45 Yeap WH, Wong KL, Shimasaki N. et al. CD16 is indispensable for antibody-dependent cellular cytotoxicity by human monocytes. Sci Rep 2016; 6: 34310
    CrossrefPubMedGoogle Scholar
  • 46 Griffith TS, Wiley SR, Kubin MZ, Sedger LM, Maliszewski CR, Fanger NA. Monocyte-mediated tumoricidal activity via the tumor necrosis factor-related cytokine, TRAIL. J Exp Med 1999; 189 (08) 1343-1354
    CrossrefPubMedGoogle Scholar
  • 47 Hartwig T, Montinaro A, von Karstedt S. et al. The TRAIL-induced cancer secretome promotes a tumor-supportive immune microenvironment via CCR2. Mol Cell 2017; 65 (04) 730-742.e5
    CrossrefPubMedGoogle Scholar
  • 48 Jaiswal S, Jamieson CH, Pang WW. et al. CD47 is upregulated on circulating hematopoietic stem cells and leukemia cells to avoid phagocytosis. Cell 2009; 138 (02) 271-285
    CrossrefPubMedGoogle Scholar
  • 49 Kuhn S, Yang J, Ronchese F. Monocyte-derived dendritic cells are essential for CD8(+) T cell activation and antitumor responses after local immunotherapy. Front Immunol 2015; 6: 584
    CrossrefPubMedGoogle Scholar
  • 50 Sheng J, Chen Q, Soncin I, Ng SL, Karjalainen K, Ruedl C. A discrete subset of monocyte-derived cells among typical conventional type 2 dendritic cells can efficiently cross-present. Cell Reports 2017; 21 (05) 1203-1214
    CrossrefPubMedGoogle Scholar
  • 51 Lopez-Yrigoyen M, Cassetta L, Pollard JW. Macrophage targeting in cancer. Ann N Y Acad Sci 2020; ;(May) DOI: 10.1111/nyas.14377.
    CrossrefPubMedGoogle Scholar
  • 52 Orecchioni M, Ghosheh Y, Pramod AB, Ley K. Macrophage polarization: different gene signatures in M1(LPS+) vs. classically and M2(LPS-) vs. alternatively activated macrophages. Front Immunol 2019; 10: 1084
    CrossrefPubMedGoogle Scholar
  • 53 Mantovani A, Sica A, Locati M. Macrophage polarization comes of age. Immunity 2005; 23 (04) 344-346
    CrossrefPubMedGoogle Scholar
  • 54 Zhou J, Tang Z, Gao S, Li C, Feng Y, Zhou X. Tumor-associated macrophages: recent insights and therapies. Front Oncol 2020; 10: 188
    CrossrefPubMedGoogle Scholar
  • 55 McGrath KE, Frame JM, Palis J. Early hematopoiesis and macrophage development. Semin Immunol 2015; 27 (06) 379-387
    CrossrefPubMedGoogle Scholar
  • 56 Arnold CE, Whyte CS, Gordon P, Barker RN, Rees AJ, Wilson HM. A critical role for suppressor of cytokine signalling 3 in promoting M1 macrophage activation and function in vitro and in vivo. Immunology 2014; 141 (01) 96-110
    CrossrefPubMedGoogle Scholar
  • 57 Murdoch C, Muthana M, Coffelt SB, Lewis CE. The role of myeloid cells in the promotion of tumour angiogenesis. Nat Rev Cancer 2008; 8 (08) 618-631
    CrossrefPubMedGoogle Scholar
  • 58 Talks KL, Turley H, Gatter KC. et al. The expression and distribution of the hypoxia-inducible factors HIF-1alpha and HIF-2alpha in normal human tissues, cancers, and tumor-associated macrophages. Am J Pathol 2000; 157 (02) 411-421
    CrossrefPubMedGoogle Scholar
  • 59 Lamouille S, Xu J, Derynck R. Molecular mechanisms of epithelial-mesenchymal transition. Nat Rev Mol Cell Biol 2014; 15 (03) 178-196
    CrossrefPubMedGoogle Scholar
  • 60 Fu XT, Dai Z, Song K. et al. Macrophage-secreted IL-8 induces epithelial-mesenchymal transition in hepatocellular carcinoma cells by activating the JAK2/STAT3/Snail pathway. Int J Oncol 2015; 46 (02) 587-596
    CrossrefPubMedGoogle Scholar
  • 61 Helm O, Held-Feindt J, Grage-Griebenow E. et al. Tumor-associated macrophages exhibit pro- and anti-inflammatory properties by which they impact on pancreatic tumorigenesis. Int J Cancer 2014; 135 (04) 843-861
    CrossrefPubMedGoogle Scholar
  • 62 Ribatti D, Tamma R, Annese T. Epithelial-mesenchymal transition in cancer: a historical overview. Transl Oncol 2020; 13 (06) 100773
    CrossrefPubMedGoogle Scholar
  • 63 Campo McKnight DA, Sosnoski DM, Koblinski JE, Gay CV. Roles of osteonectin in the migration of breast cancer cells into bone. J Cell Biochem 2006; 97 (02) 288-302
    CrossrefPubMedGoogle Scholar
  • 64 Brekken RA, Puolakkainen P, Graves DC, Workman G, Lubkin SR, Sage EH. Enhanced growth of tumors in SPARC null mice is associated with changes in the ECM. J Clin Invest 2003; 111 (04) 487-495
    CrossrefPubMedGoogle Scholar
  • 65 Zeng XY, Xie H, Yuan J. et al. M2-like tumor-associated macrophages-secreted EGF promotes epithelial ovarian cancer metastasis via activating EGFR-ERK signaling and suppressing lncRNA LIMT expression. Cancer Biol Ther 2019; 20 (07) 956-966
    CrossrefPubMedGoogle Scholar
  • 66 Yang J, Yan J, Liu B. Targeting VEGF/VEGFR to modulate antitumor immunity. Front Immunol 2018; 9: 978
    CrossrefPubMedGoogle Scholar
  • 67 Argyle D, Kitamura T. Targeting macrophage-recruiting chemokines as a novel therapeutic strategy to prevent the progression of solid tumors. Front Immunol 2018; 9: 2629
    CrossrefPubMedGoogle Scholar
  • 68 Zhao L, Lim SY, Gordon-Weeks AN. et al. Recruitment of a myeloid cell subset (CD11b/Gr1 mid) via CCL2/CCR2 promotes the development of colorectal cancer liver metastasis. Hepatology 2013; 57 (02) 829-839
    CrossrefPubMedGoogle Scholar
  • 69 Silvestre-Roig C, Fridlender ZG, Glogauer M, Scapini P. Neutrophil diversity in health and disease. Trends Immunol 2019; 40 (07) 565-583
    CrossrefPubMedGoogle Scholar
  • 70 Ng LG, Ostuni R, Hidalgo A. Heterogeneity of neutrophils. Nat Rev Immunol 2019; 19 (04) 255-265
    CrossrefPubMedGoogle Scholar
  • 71 Chatfield SM, Thieblemont N, Witko-Sarsat V. Expanding neutrophil horizons: new concepts in inflammation. J Innate Immun 2018; 10 (5-6): 422-431
    CrossrefPubMedGoogle Scholar
  • 72 Eulenberg-Gustavus C, Bähring S, Maass PG, Luft FC, Kettritz R. Gene silencing and a novel monoallelic expression pattern in distinct CD177 neutrophil subsets. J Exp Med 2017; 214 (07) 2089-2101
    CrossrefPubMedGoogle Scholar
  • 73 Sachs UJ, Andrei-Selmer CL, Maniar A. et al. The neutrophil-specific antigen CD177 is a counter-receptor for platelet endothelial cell adhesion molecule-1 (CD31). J Biol Chem 2007; 282 (32) 23603-23612
    CrossrefPubMedGoogle Scholar
  • 74 Marini O, Costa S, Bevilacqua D. et al. Mature CD10+ and immature CD10− neutrophils present in G-CSF-treated donors display opposite effects on T cells. Blood 2017; 129 (10) 1343-1356
    CrossrefPubMedGoogle Scholar
  • 75 Casanova-Acebes M, Nicolás-Ávila JA, Li JL. et al. Neutrophils instruct homeostatic and pathological states in naive tissues. J Exp Med 2018; 215 (11) 2778-2795
    CrossrefPubMedGoogle Scholar
  • 76 Cassatella MA, Östberg NK, Tamassia N, Soehnlein O. Biological roles of neutrophil-derived granule proteins and cytokines. Trends Immunol 2019; 40 (07) 648-664
    CrossrefPubMedGoogle Scholar
  • 77 Gaida MM, Steffen TG, Günther F. et al. Polymorphonuclear neutrophils promote dyshesion of tumor cells and elastase-mediated degradation of E-cadherin in pancreatic tumors. Eur J Immunol 2012; 42 (12) 3369-3380
    CrossrefPubMedGoogle Scholar
  • 78 Folco EJ, Mawson TL, Vromman A. et al. Neutrophil extracellular traps induce endothelial cell activation and tissue factor production through interleukin-1α and cathepsin G. Arterioscler Thromb Vasc Biol 2018; 38 (08) 1901-1912
    CrossrefPubMedGoogle Scholar
  • 79 Kish DD, Min S, Dvorina N, Baldwin III WM, Stohlman SA, Fairchild RL. Neutrophil cathepsin G regulates dendritic cell production of IL-12 during development of CD4 T cell responses to antigens in the skin. J Immunol 2019; 202 (04) 1045-1056
    CrossrefPubMedGoogle Scholar
  • 80 Sionov RV, Fainsod-Levi T, Zelter T, Polyansky L, Pham CT, Granot Z. Neutrophil cathepsin G and tumor cell RAGE facilitate neutrophil anti-tumor cytotoxicity. OncoImmunology 2019; 8 (09) e1624129
    CrossrefPubMedGoogle Scholar
  • 81 Wilson TJ, Nannuru KC, Futakuchi M, Singh RK. Cathepsin G-mediated enhanced TGF-beta signaling promotes angiogenesis via upregulation of VEGF and MCP-1. Cancer Lett 2010; 288 (02) 162-169
    CrossrefPubMedGoogle Scholar
  • 82 Lerchenberger M, Uhl B, Stark K. et al. Matrix metalloproteinases modulate ameboid-like migration of neutrophils through inflamed interstitial tissue. Blood 2013; 122 (05) 770-780
    CrossrefPubMedGoogle Scholar
  • 83 De Larco JE, Wuertz BR, Furcht LT. The potential role of neutrophils in promoting the metastatic phenotype of tumors releasing interleukin-8. Clin Cancer Res 2004; 10 (15) 4895-4900
    CrossrefPubMedGoogle Scholar
  • 84 Shabani F, McNeil J, Tippett L. The oxidative inactivation of tissue inhibitor of metalloproteinase-1 (TIMP-1) by hypochlorous acid (HOCI) is suppressed by anti-rheumatic drugs. Free Radic Res 1998; 28 (02) 115-123
    CrossrefPubMedGoogle Scholar
  • 85 Dumitru CA, Moses K, Trellakis S, Lang S, Brandau S. Neutrophils and granulocytic myeloid-derived suppressor cells: immunophenotyping, cell biology and clinical relevance in human oncology. Cancer Immunol Immunother 2012; 61 (08) 1155-1167
    CrossrefPubMedGoogle Scholar
  • 86 Masucci MT, Minopoli M, Carriero MV. Tumor associated neutrophils. Their role in tumorigenesis, metastasis, prognosis and therapy. Front Oncol 2019; 9: 1146
    CrossrefPubMedGoogle Scholar
  • 87 Rotondo R, Bertolotto M, Barisione G. et al. Exocytosis of azurophil and arginase 1-containing granules by activated polymorphonuclear neutrophils is required to inhibit T lymphocyte proliferation. J Leukoc Biol 2011; 89 (05) 721-727
    CrossrefPubMedGoogle Scholar
  • 88 Tecchio C, Scapini P, Pizzolo G, Cassatella MA. On the cytokines produced by human neutrophils in tumors. Semin Cancer Biol 2013; 23 (03) 159-170
    CrossrefPubMedGoogle Scholar
  • 89 Richards CD. The enigmatic cytokine oncostatin m and roles in disease. ISRN Inflamm 2013; 2013: 512103
    CrossrefPubMedGoogle Scholar
  • 90 Imai Y, Kubota Y, Yamamoto S. et al. Neutrophils enhance invasion activity of human cholangiocellular carcinoma and hepatocellular carcinoma cells: an in vitro study. J Gastroenterol Hepatol 2005; 20 (02) 287-293
    CrossrefPubMedGoogle Scholar
  • 91 Bodduluru LN, Kasala ER, Madhana RM, Sriram CS. Natural killer cells: the journey from puzzles in biology to treatment of cancer. Cancer Lett 2015; 357 (02) 454-467
    CrossrefPubMedGoogle Scholar
  • 92 Wang Y, Jönsson F. Expression, role, and regulation of neutrophil Fcγ receptors. Front Immunol 2019; 10: 1958
    CrossrefPubMedGoogle Scholar
  • 93 Artis D, Spits H. The biology of innate lymphoid cells. Nature 2015; 517 (7534): 293-301
    CrossrefPubMedGoogle Scholar
  • 94 Scoville SD, Freud AG, Caligiuri MA. Modeling human natural killer cell development in the era of innate lymphoid cells. Front Immunol 2017; 8: 360
    CrossrefPubMedGoogle Scholar
  • 95 Abel AM, Yang C, Thakar MS, Malarkannan S. Natural killer cells: development, maturation, and clinical utilization. Front Immunol 2018; 9: 1869
    CrossrefPubMedGoogle Scholar
  • 96 Melsen JE, Lugthart G, Lankester AC, Schilham MW. Human circulating and tissue-resident CD56 (bright) natural killer cell populations. Front Immunol 2016; 7: 262
    CrossrefPubMedGoogle Scholar
  • 97 Cichocki F, Sitnicka E, Bryceson YT. NK cell development and function--plasticity and redundancy unleashed. Semin Immunol 2014; 26 (02) 114-126
    CrossrefPubMedGoogle Scholar
  • 98 Malarkannan S. The balancing act: inhibitory Ly49 regulate NKG2D-mediated NK cell functions. Semin Immunol 2006; 18 (03) 186-192
    CrossrefPubMedGoogle Scholar
  • 99 Paul S, Lal G. The molecular mechanism of natural killer cells function and its importance in cancer immunotherapy. Front Immunol 2017; 8: 1124
    CrossrefPubMedGoogle Scholar
  • 100 Tallerico R, Garofalo C, Carbone E. A new biological feature of natural killer cells: the recognition of solid tumor-derived cancer stem cells. Front Immunol 2016; 7: 179
    CrossrefPubMedGoogle Scholar
  • 101 Pasero C, Gravis G, Granjeaud S. et al. Highly effective NK cells are associated with good prognosis in patients with metastatic prostate cancer. Oncotarget 2015; 6 (16) 14360-14373
    CrossrefPubMedGoogle Scholar
  • 102 Carrega P, Morandi B, Costa R. et al. Natural killer cells infiltrating human nonsmall-cell lung cancer are enriched in CD56 bright CD16(-) cells and display an impaired capability to kill tumor cells. Cancer 2008; 112 (04) 863-875
    CrossrefPubMedGoogle Scholar
  • 103 Mamessier E, Pradel LC, Thibult ML. et al. Peripheral blood NK cells from breast cancer patients are tumor-induced composite subsets. J Immunol 2013; 190 (05) 2424-2436
    CrossrefPubMedGoogle Scholar
  • 104 Carrega P, Bonaccorsi I, Di Carlo E. et al. CD56(bright)perforin(low) noncytotoxic human NK cells are abundant in both healthy and neoplastic solid tissues and recirculate to secondary lymphoid organs via afferent lymph. J Immunol 2014; 192 (08) 3805-3815
    CrossrefPubMedGoogle Scholar
  • 105 Zhang Y, Huang B. The development and diversity of ILCs, NK cells and their relevance in health and diseases. Adv Exp Med Biol 2017; 1024: 225-244
    CrossrefPubMedGoogle Scholar
  • 106 Malhotra A, Shanker A. NK cells: immune cross-talk and therapeutic implications. Immunotherapy 2011; 3 (10) 1143-1166
    CrossrefPubMedGoogle Scholar
  • 107 Ferlazzo G, Morandi B. Cross-talks between natural killer cells and distinct subsets of dendritic cells. Front Immunol 2014; 5: 159
    CrossrefPubMedGoogle Scholar
  • 108 Böttcher JP, Bonavita E, Chakravarty P. et al. NK cells stimulate recruitment of cDC1 into the tumor microenvironment promoting cancer immune control. Cell 2018; 172 (05) 1022-1037.e14
    CrossrefPubMedGoogle Scholar
  • 109 Barry KC, Hsu J, Broz ML. et al. A natural killer-dendritic cell axis defines checkpoint therapy-responsive tumor microenvironments. Nat Med 2018; 24 (08) 1178-1191
    CrossrefPubMedGoogle Scholar
  • 110 Gabrilovich DI, Nagaraj S. Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol 2009; 9 (03) 162-174
    CrossrefPubMedGoogle Scholar
  • 111 Yang Y, Li C, Liu T, Dai X, Bazhin AV. Myeloid-derived suppressor cells in tumors: from mechanisms to antigen specificity and microenvironmental regulation. Front Immunol 2020; 11: 1371
    CrossrefPubMedGoogle Scholar
  • 112 Almand B, Clark JI, Nikitina E. et al. Increased production of immature myeloid cells in cancer patients: a mechanism of immunosuppression in cancer. J Immunol 2001; 166 (01) 678-689
    CrossrefPubMedGoogle Scholar
  • 113 Gabrilovich DI, Ostrand-Rosenberg S, Bronte V. Coordinated regulation of myeloid cells by tumours. Nat Rev Immunol 2012; 12 (04) 253-268
    CrossrefPubMedGoogle Scholar
  • 114 Bronte V, Brandau S, Chen SH. et al. Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards. Nat Commun 2016; 7: 12150
    CrossrefPubMedGoogle Scholar
  • 115 Solito S, Marigo I, Pinton L, Damuzzo V, Mandruzzato S, Bronte V. Myeloid-derived suppressor cell heterogeneity in human cancers. Ann N Y Acad Sci 2014; 1319: 47-65
    CrossrefPubMedGoogle Scholar
  • 116 Kumar V, Patel S, Tcyganov E, Gabrilovich DI. The nature of myeloid-derived suppressor cells in the tumor microenvironment. Trends Immunol 2016; 37 (03) 208-220
    CrossrefPubMedGoogle Scholar
  • 117 Li Q, Pan PY, Gu P, Xu D, Chen SH. Role of immature myeloid Gr-1+ cells in the development of antitumor immunity. Cancer Res 2004; 64 (03) 1130-1139
    CrossrefPubMedGoogle Scholar
  • 118 Nagaraj S, Gabrilovich DI. Tumor escape mechanism governed by myeloid-derived suppressor cells. Cancer Res 2008; 68 (08) 2561-2563
    CrossrefPubMedGoogle Scholar
  • 119 Umansky V, Blattner C, Fleming V. et al. Myeloid-derived suppressor cells and tumor escape from immune surveillance. Semin Immunopathol 2017; 39 (03) 295-305
    CrossrefPubMedGoogle Scholar
  • 120 Bronte V, Zanovello P. Regulation of immune responses by L-arginine metabolism. Nat Rev Immunol 2005; 5 (08) 641-654
    CrossrefPubMedGoogle Scholar
  • 121 Rodriguez PC, Quiceno DG, Ochoa AC. L-arginine availability regulates T-lymphocyte cell-cycle progression. Blood 2007; 109 (04) 1568-1573
    CrossrefPubMedGoogle Scholar
  • 122 Baniyash M. TCR zeta-chain downregulation: curtailing an excessive inflammatory immune response. Nat Rev Immunol 2004; 4 (09) 675-687
    CrossrefPubMedGoogle Scholar
  • 123 Mazzoni A, Bronte V, Visintin A. et al. Myeloid suppressor lines inhibit T cell responses by an NO-dependent mechanism. J Immunol 2002; 168 (02) 689-695
    CrossrefPubMedGoogle Scholar
  • 124 Platten M, Wick W, Van den Eynde BJ. Tryptophan catabolism in cancer: beyond IDO and tryptophan depletion. Cancer Res 2012; 72 (21) 5435-5440
    CrossrefPubMedGoogle Scholar
  • 125 Munn DH, Sharma MD, Baban B. et al. GCN2 kinase in T cells mediates proliferative arrest and anergy induction in response to indoleamine 2,3-dioxygenase. Immunity 2005; 22 (05) 633-642
    CrossrefPubMedGoogle Scholar
  • 126 Frumento G, Rotondo R, Tonetti M, Damonte G, Benatti U, Ferrara GB. Tryptophan-derived catabolites are responsible for inhibition of T and natural killer cell proliferation induced by indoleamine 2,3-dioxygenase. J Exp Med 2002; 196 (04) 459-468
    CrossrefPubMedGoogle Scholar
  • 127 Mezrich JD, Fechner JH, Zhang X, Johnson BP, Burlingham WJ, Bradfield CA. An interaction between kynurenine and the aryl hydrocarbon receptor can generate regulatory T cells. J Immunol 2010; 185 (06) 3190-3198
    CrossrefPubMedGoogle Scholar
  • 128 Della Chiesa M, Carlomagno S, Frumento G. et al. The tryptophan catabolite L-kynurenine inhibits the surface expression of NKp46- and NKG2D-activating receptors and regulates NK-cell function. Blood 2006; 108 (13) 4118-4125
    CrossrefPubMedGoogle Scholar
  • 129 Ostrand-Rosenberg S, Sinha P. Myeloid-derived suppressor cells: linking inflammation and cancer. J Immunol 2009; 182 (08) 4499-4506
    CrossrefPubMedGoogle Scholar
  • 130 Hardy LL, Wick DA, Webb JR. Conversion of tyrosine to the inflammation-associated analog 3′-nitrotyrosine at either TCR- or MHC-contact positions can profoundly affect recognition of the MHC class I-restricted epitope of lymphocytic choriomeningitis virus glycoprotein 33 by CD8 T cells. J Immunol 2008; 180 (09) 5956-5962
    CrossrefPubMedGoogle Scholar
  • 131 Sinha P, Clements VK, Bunt SK, Albelda SM, Ostrand-Rosenberg S. Cross-talk between myeloid-derived suppressor cells and macrophages subverts tumor immunity toward a type 2 response. J Immunol 2007; 179 (02) 977-983
    CrossrefPubMedGoogle Scholar
  • 132 Umemura N, Saio M, Suwa T. et al. Tumor-infiltrating myeloid-derived suppressor cells are pleiotropic-inflamed monocytes/macrophages that bear M1- and M2-type characteristics. J Leukoc Biol 2008; 83 (05) 1136-1144
    CrossrefPubMedGoogle Scholar
  • 133 Berger KN, Pu JJ. PD-1 pathway and its clinical application: A 20 year journey after discovery of the complete human PD-1 gene. Gene 2018; 638: 20-25
    CrossrefPubMedGoogle Scholar
  • 134 Sinha P, Chornoguz O, Clements VK, Artemenko KA, Zubarev RA, Ostrand-Rosenberg S. Myeloid-derived suppressor cells express the death receptor Fas and apoptose in response to T cell-expressed FasL. Blood 2011; 117 (20) 5381-5390
    CrossrefPubMedGoogle Scholar
  • 135 Baniyash M. Myeloid-derived suppressor cells as intruders and targets: clinical implications in cancer therapy. Cancer Immunol Immunother 2016; 65 (07) 857-867
    CrossrefPubMedGoogle Scholar
  • 136 Jacob A, Prekeris R. The regulation of MMP targeting to invadopodia during cancer metastasis. Front Cell Dev Biol 2015; 3: 4
    CrossrefPubMedGoogle Scholar
  • 137 Vetsika EK, Koukos A, Kotsakis A. Myeloid-derived suppressor cells: major figures that shape the immunosuppressive and angiogenic network in cancer. Cells 2019; 8 (12) 1647
    CrossrefPubMedGoogle Scholar
  • 138 Martin F, Chan AC. B cell immunobiology in disease: evolving concepts from the clinic. Annu Rev Immunol 2006; 24: 467-496
    CrossrefPubMedGoogle Scholar
  • 139 Schmidt M, Böhm D, von Törne C. et al. The humoral immune system has a key prognostic impact in node-negative breast cancer. Cancer Res 2008; 68 (13) 5405-5413
    CrossrefPubMedGoogle Scholar
  • 140 Nelson BH. CD20+ B cells: the other tumor-infiltrating lymphocytes. J Immunol 2010; 185 (09) 4977-4982
    CrossrefPubMedGoogle Scholar
  • 141 de Visser KE, Korets LV, Coussens LM. De novo carcinogenesis promoted by chronic inflammation is B lymphocyte dependent. Cancer Cell 2005; 7 (05) 411-423
    CrossrefPubMedGoogle Scholar
  • 142 Ammirante M, Luo JL, Grivennikov S, Nedospasov S, Karin M. B-cell-derived lymphotoxin promotes castration-resistant prostate cancer. Nature 2010; 464 (7286): 302-305
    CrossrefPubMedGoogle Scholar
  • 143 Mizoguchi A, Mizoguchi E, Takedatsu H, Blumberg RS, Bhan AK. Chronic intestinal inflammatory condition generates IL-10-producing regulatory B cell subset characterized by CD1d upregulation. Immunity 2002; 16 (02) 219-230
    CrossrefPubMedGoogle Scholar
  • 144 Wei X, Jin Y, Tian Y. et al. Regulatory B cells contribute to the impaired antitumor immunity in ovarian cancer patients. Tumour Biol 2016; 37 (05) 6581-6588
    CrossrefPubMedGoogle Scholar
  • 145 Wang WW, Yuan XL, Chen H. et al. CD19+CD24hiCD38hiBregs involved in downregulate helper T cells and upregulate regulatory T cells in gastric cancer. Oncotarget 2015; 6 (32) 33486-33499
    CrossrefPubMedGoogle Scholar
  • 146 Carter NA, Vasconcellos R, Rosser EC. et al. Mice lacking endogenous IL-10-producing regulatory B cells develop exacerbated disease and present with an increased frequency of Th1/Th17 but a decrease in regulatory T cells. J Immunol 2011; 186 (10) 5569-5579
    CrossrefPubMedGoogle Scholar
  • 147 Inoue S, Leitner WW, Golding B, Scott D. Inhibitory effects of B cells on antitumor immunity. Cancer Res 2006; 66 (15) 7741-7747
    CrossrefPubMedGoogle Scholar
  • 148 Rubtsov AV, Rubtsova K, Kappler JW, Jacobelli J, Friedman RS, Marrack P. CD11c-expressing B cells are located at the T cell/B cell border in spleen and are potent APCs. J Immunol 2015; 195 (01) 71-79
    CrossrefPubMedGoogle Scholar
  • 149 Nielsen JS, Sahota RA, Milne K. et al. CD20+ tumor-infiltrating lymphocytes have an atypical CD27- memory phenotype and together with CD8+ T cells promote favorable prognosis in ovarian cancer. Clin Cancer Res 2012; 18 (12) 3281-3292
    CrossrefPubMedGoogle Scholar
  • 150 Largeot A, Pagano G, Gonder S, Moussay E, Paggetti J. The B-side of cancer immunity: the underrated tune. Cells 2019; 8 (05) x
    CrossrefPubMedGoogle Scholar
  • 151 Germain C, Gnjatic S, Tamzalit F. et al. Presence of B cells in tertiary lymphoid structures is associated with a protective immunity in patients with lung cancer. Am J Respir Crit Care Med 2014; 189 (07) 832-844
    CrossrefPubMedGoogle Scholar
  • 152 Kurts C, Carbone FR, Barnden M. et al. CD4+ T cell help impairs CD8+ T cell deletion induced by cross-presentation of self-antigens and favors autoimmunity. J Exp Med 1997; 186 (12) 2057-2062
    CrossrefPubMedGoogle Scholar
  • 153 Josefowicz SZ, Lu LF, Rudensky AY. Regulatory T cells: mechanisms of differentiation and function. Annu Rev Immunol 2012; 30: 531-564
    CrossrefPubMedGoogle Scholar
  • 154 Bennett SR, Carbone FR, Karamalis F, Flavell RA, Miller JF, Heath WR. Help for cytotoxic-T-cell responses is mediated by CD40 signalling. Nature 1998; 393 (6684): 478-480
    CrossrefPubMedGoogle Scholar
  • 155 Bullock TN, Yagita H. Induction of CD70 on dendritic cells through CD40 or TLR stimulation contributes to the development of CD8+ T cell responses in the absence of CD4+ T cells. J Immunol 2005; 174 (02) 710-717
    CrossrefPubMedGoogle Scholar
  • 156 Ahrends T, Spanjaard A, Pilzecker B. et al. CD4+ T cell help confers a cytotoxic T cell effector program including coinhibitory receptor downregulation and increased tissue invasiveness. Immunity 2017; 47 (05) 848-861.e5
    CrossrefPubMedGoogle Scholar
  • 157 Castellino F, Huang AY, Altan-Bonnet G, Stoll S, Scheinecker C, Germain RN. Chemokines enhance immunity by guiding naive CD8+ T cells to sites of CD4+ T cell-dendritic cell interaction. Nature 2006; 440 (7086): 890-895
    CrossrefPubMedGoogle Scholar
  • 158 Greyer M, Whitney PG, Stock AT. et al. T cell help amplifies innate signals in CD8(+) DCs for optimal CD8(+) T cell priming. Cell Reports 2016; 14 (03) 586-597
    CrossrefPubMedGoogle Scholar
  • 159 Filatenkov AA, Jacovetty EL, Fischer UB, Curtsinger JM, Mescher MF, Ingulli E. CD4 T cell-dependent conditioning of dendritic cells to produce IL-12 results in CD8-mediated graft rejection and avoidance of tolerance. J Immunol 2005; 174 (11) 6909-6917
    CrossrefPubMedGoogle Scholar
  • 160 Zanetti M. Tapping CD4 T cells for cancer immunotherapy: the choice of personalized genomics. J Immunol 2015; 194 (05) 2049-2056
    CrossrefPubMedGoogle Scholar
  • 161 Takeuchi A, Saito T. CD4 CTL, a cytotoxic subset of CD4+ T cells, their differentiation and function. Front Immunol 2017; 8: 194
    CrossrefPubMedGoogle Scholar
  • 162 Braumüller H, Wieder T, Brenner E. et al. T-helper-1-cell cytokines drive cancer into senescence. Nature 2013; 494 (7437): 361-365
    CrossrefPubMedGoogle Scholar
  • 163 Bos R, Sherman LA. CD4+ T-cell help in the tumor milieu is required for recruitment and cytolytic function of CD8+ T lymphocytes. Cancer Res 2010; 70 (21) 8368-8377
    CrossrefPubMedGoogle Scholar
  • 164 Matsuzaki J, Tsuji T, Luescher IF. et al. Direct tumor recognition by a human CD4(+) T-cell subset potently mediates tumor growth inhibition and orchestrates anti-tumor immune responses. Sci Rep 2015; 5: 14896
    CrossrefPubMedGoogle Scholar
  • 165 Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science 2003; 299 (5609): 1057-1061
    CrossrefPubMedGoogle Scholar
  • 166 Vignali DA, Collison LW, Workman CJ. How regulatory T cells work. Nat Rev Immunol 2008; 8 (07) 523-532
    CrossrefPubMedGoogle Scholar
  • 167 Frydrychowicz M, Boruczkowski M, Kolecka-Bednarczyk A, Dworacki G. The dual role of Treg in cancer. Scand J Immunol 2017; 86 (06) 436-443
    CrossrefPubMedGoogle Scholar
  • 168 Hindley JP, Ferreira C, Jones E. et al. Analysis of the T-cell receptor repertoires of tumor-infiltrating conventional and regulatory T cells reveals no evidence for conversion in carcinogen-induced tumors. Cancer Res 2011; 71 (03) 736-746
    CrossrefPubMedGoogle Scholar
  • 169 Walker LS. Treg and CTLA-4: two intertwining pathways to immune tolerance. J Autoimmun 2013; 45: 49-57
    CrossrefPubMedGoogle Scholar
  • 170 Liang B, Workman C, Lee J. et al. Regulatory T cells inhibit dendritic cells by lymphocyte activation gene-3 engagement of MHC class II. J Immunol 2008; 180 (09) 5916-5926
    CrossrefPubMedGoogle Scholar
  • 171 Cao X, Cai SF, Fehniger TA. et al. Granzyme B and perforin are important for regulatory T cell-mediated suppression of tumor clearance. Immunity 2007; 27 (04) 635-646
    CrossrefPubMedGoogle Scholar
  • 172 Deaglio S, Dwyer KM, Gao W. et al. Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression. J Exp Med 2007; 204 (06) 1257-1265
    CrossrefPubMedGoogle Scholar
  • 173 Jarnicki AG, Lysaght J, Todryk S, Mills KH. Suppression of antitumor immunity by IL-10 and TGF-beta-producing T cells infiltrating the growing tumor: influence of tumor environment on the induction of CD4+ and CD8+ regulatory T cells. J Immunol 2006; 177 (02) 896-904
    CrossrefPubMedGoogle Scholar
  • 174 Yu P, Lee Y, Liu W. et al. Intratumor depletion of CD4+ cells unmasks tumor immunogenicity leading to the rejection of late-stage tumors. J Exp Med 2005; 201 (05) 779-791
    CrossrefPubMedGoogle Scholar
  • 175 Facciabene A, Peng X, Hagemann IS. et al. Tumour hypoxia promotes tolerance and angiogenesis via CCL28 and T(reg) cells. Nature 2011; 475 (7355): 226-230
    CrossrefPubMedGoogle Scholar