Tfh cells potential dual role in cancer: A perspective

T follicular helper cells (Tfh) were initially identified nearly two decades ago as critically important in directing B-cell maturation and antibody generation in the germinal centers of secondary lymphoid tissues. Since then, Tfh cells have become the center of sustained investigation in oncology due to their unique, often paradoxical roles in tumour immunity. Specifically, Tfh cells in the tumour microenvironment can enhance anti-tumour immune response or promote, through the same mechanisms, tumour progression. These dual roles largely result from Tfh cells controlling unique cytokine secretions and, in turn, shifting the net effect of the Tfh-driven immune response (by directly and indirectly affecting the activities of other cytotoxic T cells and natural killer cells). The dual nature of the Tfh is the basis for our commentary, which highlights their simultaneous identity as a curse and a gift to oncology. Indeed, the curtain calls for a better understanding Tfh cell biology, so that their potential can be used to benefit oncology. We discuss how prevalent Tfh cells in tumors can be beneficial in directing potent anti-tumour immune responses. We also review how the characterization of Tfh cells in tumors has now led to their identification as candidate biomarkers of response to immunotherapy, and how they are now being evaluated as targets for new immunotherapies leading to new clinical trials. The study concludes by emphasizing how the unique biological properties of Tfh cells can be leveraged to advance cancer treatment, ultimately aiming to enhance the effectiveness of clinical oncology practices.