Targeting the tumor microenvironment and T cell metabolism for effective cancer immunotherapy.

The successful implementation of immunotherapies has provided new impetus in the fight against cancer. Antibody-mediated blockade of immune checkpoint molecules PD-1/PD-L1 and CTLA-4 has had a dramatic impact upon the treatment of previously intractable cancers such as malignant melanoma, while adoptive cell therapies using chimeric antigen receptor-bearing T cells have proven highly efficacious in B cell leukemia. Furthermore, significant progress has been made in understanding the mechanisms by which tumors evade or become resistant to these immunotherapies. In this regard, approaches to broaden the applicability and enhance the efficacy of immunotherapies increasingly include modulation of tumor and immune cell metabolism. In this mini-review, we highlight the most recent studies describing novel approaches and targets for the manipulation of the tumor microenvironment and T cell metabolism and describe how these approaches are being combined with current immunotherapies in preclinical studies.