Immuncheckpoint-Inhibition

Die Immuncheckpoint-Inhibition ist eine vielversprechende Behandlungsstrategie in der Onkologie. Immuncheckpoint-Inhibitoren, zumeist monoklonale Antikörper, blockieren die inhibitorischen Signale des Immunsystems und verstärken so die Immunantwort gegen den Tumor. Dieser Übersichtsartikel vermittelt grundlegendes Wissen über die Immuncheckpoint-Inhibition und zeigt den aktuellen Stellenwert dieser Therapien in der modernen Krebstherapie.

Abstract

Immune checkpoint inhibition is now a well-established treatment strategy in cancer therapy. Immune checkpoint inhibitors, mostly monoclonal antibodies, block the inhibitory signals of the immune system and thus enhance the immune response against the tumour. Immune checkpoint inhibitors have become an integral part of modern oncology. Their almost ubiquitous use in cancers of all organ systems shows that the pathological entity of the tumour disease is playing an increasingly subordinate role in the use of immune checkpoint inhibition and that the immunological view in oncology is gaining in importance. Modern biomarkers for the prediction of ICI efficacy and tumour resistance are being developed to improve therapeutic stratification. Future challenges include the management of autoimmune side effects and the combination of checkpoint therapies with other immunotherapies such as mRNA vaccination or CAR-T cell therapy.

Schlüsselwörter

Immuncheckpoint-Inhibition - Tumorimmunologie - Tumormikromiiieu

Keywords

immune checkpoint inhibition - cancer immunology - tumour micromillieu

• Literatur

• 1 Doroshow DB, Bhalla S, Beasley MB. et al. PD-L1 as a biomarker of response to immune-checkpoint inhibitors. Nat Rev Clin Oncol 2021; 18: 345-62
• 2 Chowell D, Yoo S-K, Valero C. et al. Improved prediction of immune checkpoint blockade efficacy across multiple cancer types. Nat Biotechnol 2022; 40: 499—506
• 3 Havel JJ, Chowell D, Chan TA. The evolving landscape of biomarkers for checkpoint inhibitor immunotherapy. Nat Rev Cancer 2019; 19: 133-50
• 4 Bai R, Lv Z, Xu D. et al. Predictive biomarkers for cancer immunotherapy with immune checkpoint inhibitors. Biomark Res 2020; 8: 34
• 5 Samstein RM, Lee C-H, Shoushtari AN. et al. Tumor mutational load predicts survival after immunotherapy across multiple cancer types. Nat Genet 2019; 51: 202-6
• 6 Rizvi H, Sanchez-Vega F, La K. et al. Molecular determinants of response to anti-programmed cell death (pd)-1 and anti–programmed death-ligand 1 (PD-L1) blockade in patients with non–small-cell lung cancer profiled with targeted next-generation sequencing. JCO 2018; 36: 633-41
• 7 Chen DS, Mellman I. Elements of cancer immunity and the cancer–immune set point. Nature 2017; 541: 321-30
• 8 Schenkel JM, Pauken KE. Localization, tissue biology and T cell state — implications for cancer immunotherapy. Nat Rev Immunol 2023;
• 9 Derosa L, Routy B, Thomas AM. et al. Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non-small-cell lung cancer. Nat Med 2022; 28: 315-24
• 10 Derosa L, Hellmann MD, Spaziano M. et al. Negative association of antibiotics on clinical activity of immune checkpoint inhibitors in patients with advanced renal cell and non-small-cell lung cancer. Annals of Oncology 2018; 29: 1437-44
• 11 Routy B, Lenehan JG, Miller WH. et al. Fecal microbiota transplantation plus anti-PD-1 immunotherapy in advanced melanoma: a phase I trial. Nat Med 2023;
• 12 Dougan M, Luoma AM, Dougan SK. et al. Understanding and treating the inflammatory adverse events of cancer immunotherapy. Cell 2021; 184: 1575-88
• 13 Stamatouli AM, Quandt Z, Perdigoto AL. et al. Collateral damage: insulin-dependent diabetes induced with checkpoint inhibitors. Diabetes 2018; 67: 1471-80
• 14 Sullivan RJ, Weber JS. Immune-related toxicities of checkpoint inhibitors: mechanisms and mitigation strategies. Nat Rev Drug Discov 2022; 21: 495-508
• 15 Johnson DB, Nebhan CA, Moslehi JJ. et al. Immune-checkpoint inhibitors: long-term implications of toxicity. Nat Rev Clin Oncol 2022;
• 16 Wherry EJ, Kurachi M. Molecular and cellular insights into T cell exhaustion. Nat Rev Immunol 2015; 15: 486-99
• 17 Aggarwal V, Workman CJ, Vignali DAA. LAG-3 as the third checkpoint inhibitor. Nat Immunol 2023;
• 18 Waldman AD, Fritz JM, Lenardo MJ. A guide to cancer immunotherapy: from T cell basic science to clinical practice. Nat Rev Immunol 2020; 20: 651-68
• 19 Winship AL, Alesi LR, Sant S. et al. Checkpoint inhibitor immunotherapy diminishes oocyte number and quality in mice. Nat Cancer 2022; 3: 1-13
• 20 Jiang P, Sinha S, Aldape K. et al. Big data in basic and translational cancer research. Nat Rev Cancer 2022; 22: 625-39
• 21 Weilandt J, Lebahn H, Ludwig-Peitsch W. Chemotherapy following progression after immune checkpoint inhibition in metastasizing malignant melanoma: Case report and Literature Review. Aktuelle Dermatologie 2022; 48: 458-464