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Gene expression profiling of tumor-infiltrating CD45+CD8+ cells and CD45- tumor cells of tumor bearing mice treated with metformin or anti-PD-1 Ab or both

ABSTRACT: B16 Mouse melanoma cells (MO5) grow in syngeneic C57BL/6 mice. Anti-PD-1 Ab as an Immunecheck point inhibitor and/or metformin were administered on day 7 after tumor inoculation to mice. The tumor growth was decreased by either anti-PD-1 Ab or metformin treatment. Anti- tumor effect was more pronounced by the combination therapy of anti-PD-1 Ab and metformin. The mechanism underlying the superior effect of the combination therapy to mono-therapies were investigated by RNA sequencing of tumor infiltrating CD8+ cells (CD8TILs) and tumor cells. As a result, CD8TILs with the combination therapy was found to express IFNg and GzmB and to activate IRF1/8, STAT1/2, NFkB, TBX21. Moreover, tumor cells were found to activate IRF1/8, STAT1/2, NFkB, indicating that tumor cells sharply responded to IFNg produced from CD8TILs. The IFNg was also found to downregulate metabolism both glycolysis and oxidative phosphorylation (OxPhos) of tumor cells, while it upregulates metabolism of CD8T cells. Collectively, the metabolic competition between CD8TILs and tumor cells was found to shift to the advantage of CD8TILs over tumor cells, resulting in the strong inhibition of tumor growth by the combination therapy of anti-PD-1 Ab and metformin.

ORGANISM(S): Mus musculus

PROVIDER: GSE134191 | GEO | 2022/07/01

REPOSITORIES: GEO

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