CD4 and neoplasm: During the tumor progression, the immune cell populations changed overtime, for example, in the early stages of ESCC, non-tumor regions are predominantly enriched with naïve CD4+ T cells, memory CD4+ T cells, and Th17 cells, whereas tumor regions are characterized by an increased presence of regulatory T cells (Tregs), cytotoxic T cells, and pre-terminal exhausted T cells (Yao et al., 2020; Zheng et al., 2020; Chen et al., 2021b; Dinh et al., 2021).