However, despite its potential, CAR-T-cell therapy targeting CSCs presents several challenges, including tumor heterogeneity, antigen escape, and an immunosuppressive TME, all of which limit its therapeutic efficacy.396,397 CSCs secrete immunosuppressive cytokines, such as TGF-β and IL-33, which suppress T-cell activity while also upregulating PD-L1 expression, leading to CAR-T-cell exhaustion.398,399 These barriers necessitate the development of next-generation CAR-T-cell strategies that can overcome these immune evasion mechanisms. The gene discussed is TGFB1; the disease is neoplasm.