Pancreatic cancer alters human CD4+ T lymphocyte function: a piece in the immune evasion puzzle.

Objectives: To verify whether the dysregulation of CD4(+) T cells concurs in worsening the outcome of pancreatic cancer, we compared the effects of pancreatic cancer and other gastrointestinal cancer cell-conditioned media on the (1) proliferation, migration, and differentiation of CD4(+) T cells and (2) expansion of CD4(+) memory (CD45RO), naive (CD45RA), activated (CD69), and regulatory (CD25) subsets. Methods: After culture of CD4(+) T cells in control, pancreatic (BxPC3, Capan1, MiaPaCa2), or gastrointestinal cancer (AGS, HepG2, HT29) cell-conditioned media, we evaluated proliferation, migration, interferon gamma (IFN gamma) production, and CD45RA, CD45RO, CD69, and CD25 membrane expression in control and conditioned CD4(+) T cells. Results: Only pancreatic cancer-conditioned media (1) inhibited CD4(+) T-cell proliferation (P < 0.001) and migration under human stromal cell-derived factor-alpha chemotaxis (P < 0.001) and (2) induced CD4(+) T-cell IFN gamma production (P < 0.05) and the expansion of the CD69-positive subset (P < 0.001) with respect to the control, with no changes being found in the CD45RA, CD45RO, and CD25 subsets. Conclusions: The in vitro findings achieved in the present study demonstrate that pancreatic cancer cells inhibit CD4(+) T-cell proliferation and migration, induce IFN gamma production, and favor a CD69(+) subset expansion, suggesting that CD4(+) T cells play an important role in pancreatic cancer immune evasion.