Janus or Hydra: The Many Faces of T Helper Cells in the Human Tumour Microenvironment.

CD4+ T helper (T) cells are key regulators in the tumour immune microenvironment (TIME), mediating the adaptive immunological response towards cancer, mainly through the activation of cytotoxic CD8+ T cells. After antigen recognition and proper co-stimulation, naïve T cells are activated, undergo clonal expansion, and release cytokines that will define the differentiation of a specific effector T cell subtype. These different subtypes have different functions, which can mediate both anti- and pro-tumour immunological responses. Here, we present the dual role of T cells restraining or promoting the tumour, the factors controlling their homing and differentiation in the TIME, their influence on immunotherapy, and their use as prognostic indicators.