Table 1 Possible combination therapy for these immunophenotypes of TME with different immune feature

Cold tumor

T cell deficiency, low tumor mutational burden, and poor antigen presentation [168]

Promote cancer ferroptosis to heat cancer and combine with immunotherapy like ICB.

Immune-suppressive tumor

Full of immunosuppressive cells like MDSCs, Tregs, and M2-type TAMs with local adaptive immunosuppression [243]

Combine immunotherapy with ferroptosis therapy targeting immunosuppressive cells, especially MDSCs, and M2-TAMs.

Immune-excluded tumor

ECM, hypoxia, and deficient chemokines inhibiting the recruitment of T cells and establishing immunosuppression [168]

Need more investigation. HIFs inhibitors combined with ferroptosis therapy and chemokines may be an optional method.

Hot tumor

Adequate infiltration of anti-cancer T cells in the center of TME [244]

Combine with ferroptosis therapy when drug resistance to immunotherapy occurs, especially for cancer cells with dedifferentiated phenotypes.