T follicular helper and T follicular regulatory cells in colorectal cancer: A complex interplay

Colorectal cancer is considered to be one of the major causes of morbidity and mortality all over the world. T Follicular helper (TFH) and T follicular regulatory (TFR) cells are specialized providers of T-cells to help B-cells and shaping germinal centers (GC) response. Recent researches reported a high percentage of TFH and TFR in different infectious diseases and certain malignancies. However, their functional role in human colorectal cancer (CRC) is relatively unknown. Furthermore, recent studies show that the interaction of both TFH cells and TFR cells are essential to promote several diseases. Under the control of specific cytokines and B-cell lymphoma 6 transcription factor (Bcl-6), the major transcription factor of TFH cells, TFH, can expand to the other distinct CD4 + T helper cells (TH1, TH2, and TH17) which exert a different role in the development of CRC. This review aims to discuss these suggested roles of the two-opposite subset of follicular T cells in colorectal cancer immune pathogenesis.