Many factors contributed to the resistance to ICI therapy, which includes the T cells exclusion and dysfunction in the TME, defects in antigen processing and lack of tumor-associated antigens, presence of alternative inhibitory immune checkpoints (such as VISTA, TIM-3, LAG-3, and TIGIT), as well as the tumor-cell extrinsic factors such as immunosuppressive cells (Tregs, TAMs) and inhibitory cytokines (TGF-β) (so-called “cold” tumors). The gene discussed is TGFB1; the disease is neoplasm.