Ammonia Suppresses the Antitumor Activity of Natural Killer Cells and T Cells by Decreasing Mature Perforin.

ABSTRACT: Immunotherapy revolutionized cancer treatment in the last decade. Both NK cells and T cells are key components of host immunity against malignant cells that are being extensively investigated in the field of cancer immunotherapy. While approaches have been developed to improve the antitumor activity of NK and T cells, the tumor microenvironment remains an obstacle to effective NK and T-cell-based therapies. Here, we demonstrated that cancer-conditioned medium suppresses the antitumor activity of NK cells. Ammonia, a by-product of cancer cell metabolism, accumulated in cancer-conditioned medium and in the tumor microenvironment, and impaired the cytotoxicity of NK cells as well as the efficacy of antibody-based and chimeric antigen receptor (CAR) NK and CAR T-cell-based therapies in vitro.

SUBMITTER: Domagala J 

PROVIDER: S-EPMC12214879 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature