CD4 and neoplasm: Based on these characteristics, we hypothesized that old IEL CD4, like nIELs and CD8αα+CD4+ T cells, may play an important role in anti-tumor immunity and intestinal immune homeostasis via cytotoxic activity, and performed functional analysis in vitro. Although IEL CD4+ T cells alone showed low cytotoxic activity, old IEL CD3+ T cells showed higher cytotoxic activity against tumor organoids than that of young IEL CD3+ T cells.