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Molecular Biology and Functions of T Follicular Helper Cells in Cancer and Immunotherapy

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T follicular helper (Tfh) cells are integral to the germinal center (GC) response and the development of potent humoral immunity. By priming B cells, Tfh cells can initiate both extrafollicular and GC-dependent Ab responses. The dynamic physical interactions between Tfh and B cells constitute the primary platform for Tfh cells to provide essential "help" factors to B cells, as well as for reciprocal signaling from B cells to sustain the helper state of Tfh cells. In recent years, significant advancements have been made in understanding the diverse roles of Tfh cells across various diseases, particularly in cancer. Notably, beyond the classical GC-Tfh cells, it is increasingly recognized that the Tfh cell phenotype is highly heterogeneous and dynamic, which adds complexity to their roles in disease contexts. This review aims to encapsulate progress in Tfh cell biology, with a focus on their role in cancer and immunotherapy.

Abstract

T follicular helper (Tfh) cells are integral to the germinal center (GC) response and the development of potent humoral immunity. By priming B cells, Tfh cells can initiate both extrafollicular and GC-dependent Ab responses. The dynamic physical interactions between Tfh and B cells constitute the primary platform for Tfh cells to provide essential "help" factors to B cells, as well as for reciprocal signaling from B cells to sustain the helper state of Tfh cells. In recent years, significant advancements have been made in understanding the diverse roles of Tfh cells across various diseases, particularly in cancer. Notably, beyond the classical GC-Tfh cells, it is increasingly recognized that the Tfh cell phenotype is highly heterogeneous and dynamic, which adds complexity to their roles in disease contexts. This review aims to encapsulate progress in Tfh cell biology, with a focus on their role in cancer and immunotherapy.

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