American Association for Cancer Research
Browse
23266066cir180222-sup-199734_3_supp_5184354_pwtdww.pdf (446.5 kB)

Figure S3 from Late-Stage Tumor Regression after PD-L1 Blockade Plus a Concurrent OX40 Agonist

Download (446.5 kB)
journal contribution
posted on 2023-04-03, 23:29 authored by Fanny Polesso, Andrew D. Weinberg, Amy E. Moran

Figure S3 shows the therapeutic efficacy of combination therapy in the absence of CD4 or CD8 T cells.

Funding

American Cancer Society

NIH

History

ARTICLE ABSTRACT

The protective capability of tumor antigen–specific T cells is regulated by costimulatory and inhibitory signals. Current approaches in cancer immunotherapy seek to restore the function of unresponsive T cells by blocking inhibitory pathways. In contrast, providing exogenous costimulatory signals to T cells also enhances antitumor functionality. By combining these two clinical approaches, we demonstrate the synergy of targeting PD-L1 together with the costimulatory molecule OX40, to enhance antitumor immunity. Concurrently blocking PD-L1 and providing a costimulatory agonist to OX40 increased the presence and functionality of tumor antigen–specific CD8+ T cells with simultaneous enhancement of T-helper type 1 (Th1)-skewed CD4+ T cells. This shift was functionally supported by increased glucose metabolism of antigen-specific CD8+ T cells and the acquisition of granzyme B by regulatory T cells. Together, this mechanism promoted tumor regression of late-stage tumors beyond that achieved by either blockade as monotherapy. These findings indicate that targeting both T-cell intrinsic (OX40) and extrinsic (PD-L1) regulatory molecules increases the bioenergetic potential of T cells, thereby expanding functional and tumor antigen–specific T cells.

Usage metrics

    Cancer Immunology Research

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC