CD4 and neoplasm: Conversely, resistance to ICIs may develop due to compensatory Treg proliferation or the upregulation of alternative checkpoint molecules on these cells.98 A study involving bladder cancer patients who underwent radical cystectomy revealed a higher frequency of CD4+ Tregs, identified by high expression of CD4, CD25, FOXP3, and low/neg CD127 expression, in tumor-draining lymph nodes in cases of advanced-stage disease.99 These findings suggest that Tregs may hinder anti-tumor immune responses, highlighting their potential impact on the effectiveness of immunotherapy in bladder cancer treatment.