<p>Crosstalk between the nervous system and the immune system shapes the tumor microenvironment. Cholinergic T cells, a unique population of T cell antigen receptor-induced acetylcholine-producing T cells, have emerged as an integrative interface between these two fundamental body systems. Here we review the distinct characteristics and functions of cholinergic T cells in cancer settings. We first outline the expression of choline acetyltransferase and the cholinergic machinery in T cells. We then describe the dysfunctional state of choline acetyltransferase-expressing T cells in cancer and delve into their modulatory effects on T cells, cancer cells and the tumor microenvironment, including its populations of immune cells, its vasculature and its nerves. We also discuss the clinical implications of harnessing the potential of cholinergic T cells and future directions for increasing our understanding of their importance and possible exploitation.</p>