CD4 and neoplasm: Recent preclinical studies have highlighted the potential for cytokine-based immunotherapies to synergize with immune checkpoint inhibitors: a preclinical study by Wu et al. on the combination of IL-21 and anti-PD-1 therapy demonstrated that IL-21, produced by tumor-associated T follicular helper cells and exhausted CD4+ T cells, can significantly enhance the antitumor effects of PD-1 blockade [41].