We speculated that these inconsistencies could be attributed to the different tumor microenvironment contexts, IL-21 has been proposed acting in a context-dependent manner (27), therefore while presence of IL-21 provide a valid explanation for the activation of T or B cells in tumor tissue, a variety of cofactors e.g., PD-L1, CTLA-4 and tumor-derived factors may influence IL-21 actions. Here, CTLA4 is linked to neoplasm.