Controversial role of γδ T cells in pancreatic cancer

gamma delta T cells are rare lymphocytes with cogent impact on immune responses. These cells are one of the earliest cells to be recruited in the sites of infection or tumors and play a critical role in coordinating innate and adaptive immune responses. The anti-tumor activity of gamma delta T cells have been numerously reported; nonetheless, there is controversy among published studies regarding their anti-tumor vs pro-tumor effect-especially in pancreatic cancer. A myriad of studies has confirmed that activated gamma delta T cells can potently lyse a broad variety of solid tumors and leukemia/lymphoma cells and produce an array of cytokines; however, early gamma delta T cell-based clinical trials did not lead to optimal efficacy, despite acceptable safety. Depending on the local micromilieu, gamma delta T cells can differentiate into tumor promoting or suppressing cells such as Th1-, Th2-, or Th17-like cells and produce prototypical cytokines such as interferon-gamma (IFN gamma) and interleukin (IL)-4/-10, IL-9, or IL-17. In an abstruse tumor such as pancreatic cancer-also known as immunologically cold tumor-gamma delta T cells are more likely to switch to their immunosuppressive phenotype. In this review we will adduce the accumulated knowledge on these two controversial aspects of gamma delta T cells in cancers-with a focus on solid tumors and pancreatic cancer. In addition, we propose strategies for enhancing the anti-tumor function of gamma delta T cells in cancers and discuss the potential future directions.

Automated summary

γδT cells are rare lymphocytes that play a cogent role in immune responses. They have anti-tumor activity, but there is controversy regarding their effects in pancreatic cancer. Depending on the local microenvironment, γδT cells can differentiate into cells that promote or suppress tumors. In immunologically cold tumors like pancreatic cancer, γδT cells are more likely to exhibit an immunosuppressive phenotype.