CD4 and neoplasm: Cancer immunotherapy has achieved impressive success in the treatment of solid and hematological metastatic malignant tumors.1–4 The tumor microenvironment (TME) induces T cell dysfunction by attenuating the signal transduction of the T cell receptor.5–7 Immune checkpoint inhibitor (ICI) targeted therapies reinvigorate antitumor immune responses by recovering the function of tumor infiltrating T cells (TILs) such as CD4, CD8, and γδ T cells in the TME.4,8–12 However, only a sizable minority of cancer patients respond to ICI therapy.