CD8A and neoplasm: One of the main factors contributing to primary resistance to ICIs is the lack of tumor-infiltrating T cells, which is one of the characteristics of “cold” tumors whose TME is infiltrated with various immunosuppressive cells such as stromal cells, M2 macrophages, MDSCs, and Treg cells.407,408 ICIs may be most effective when in combination with therapies that increase the amount of CD8+ T cells for the treatment of cold tumors.