Targeting immunosuppressive tumor microenvironment to combat immunotherapy resistance: From mechanistic insights to therapeutic strategies.

With advances in deciphering the intricate interplay between tumors and the immune system, tumor immunotherapy has flourished significantly and has revolutionized conventional tumor therapies, owing to its durable immunological memory and favorable safety profile. Nevertheless, immunotherapy is not currently beneficial for all patients, largely due to the immunosuppressive tumor microenvironment (TME). Considerable efforts have been devoted to bolstering the efficacy of immunotherapy by remodeling the TME. Effective remodeling of the TME and the associated reversal of immunosuppressive conditions indicate the potential value of targeting the TME in tumor immunotherapy. Herein, we first elaborate on several mechanisms underlying the formation of immunosuppressive TME based on current evidence and highlight the major obstacles to successful immunotherapy. Subsequently, a variety of strategies concerning remodeling immunosuppressive TME and improving immunotherapeutic efficacy are summarized, and the remaining challenges and future perspectives in the development of antitumor immunotherapy are discussed. Hopefully, the development of immunotherapy will invigorate the further exploration of comprehensive tumor therapy.