Interleukin-3 producing B cells amplifies the development and progression of pancreatic ductal adenocarcinoma

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with one of the lowest 5-year survival rates of all solid tumors. Although multiple therapeutic strategies have been explored to improve the survival of PDAC patients, the outcome is still limited. In this study, we sought to investigate the importance of interleukin-3 (IL-3), a hematopoietic growth factor, master regulator of inflammation, mainly produced by T and B cells and its impact on the lymphatic microenvironment during pancreatic cancer disease.

Methods: Human – We employed ECLipse, qPCR, Flow Cytometry and Immunohistochemistry on pre-surgical peripheral blood and lymph node samples from PDAC and Cholecystectomy (control) patients ([Fig. 2]). Murine – Orthotopic injection of murine pancreatic cancer cell line (TB32047) in IL-3 deficient mice was performed to understand the role of IL-3 in tumor progression and survival.

Results Our results demonstrate increased relative mRNA expression ([Fig. 1a]) and serum IL-3 level ([Fig. 1b]) in PDAC patients than control patients. PDAC patients with perineural invasion (Pn) and higher grading (G3) had increased serum IL-3 level than Pn0 and G2 ([Fig. 1c, d]). Neoadjuvant treatment significantly decreased serum IL-3 level ([Fig. 1e]). LN of PDAC patients had significantly increased B cells and IL3+B cells than LN of control patients. LN8a with tumor infiltration had increased IL3+B cells, proliferating B cells, and decreased expression of Blimp1. Neoadjuvant treatment to PDAC patients resulted in decreased lymphatic B cells and IL3+B cells than non-treated patients. Using mouse model we show that IL-3 potentiates the development and progression of pancreatic cancer. IL-3 deficiency resulted in better survival, shrinkage of pancreas tumour, decreased the number of B cells, decreased serum IL-6 and increased the frequencies of Blimp1 in the lymphatic environment.

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Conclusion: Our results identify a previously unrecognized role of IL-3 producing B cells in the development and progression of pancreatic cancer and underscore the potential significance of B cell/IL-3 axis as a therapeutic target.

Publication History

Article published online:
28 August 2023