CD40 agonism improves anti-tumor T cell priming induced by the combination of radiation therapy plus CTLA4 inhibition and enhances tumor response

ABSTRACT

Radiation therapy (RT) combined with CTLA4 blockers converts immunosuppressed (cold) mouse triple negative breast cancers (TNBCs) into immune infiltrated (hot) lesions. We have recently shown that targeting the myeloid compartment to improve dendritic cell activation is required for most TNBC-bearing mice to achieve superior therapeutic responses to RT plus CTLA4 inhibitors.

KEYWORDS:

• In situ vaccination
• immune checkpoint inhibitors
• dendritic cells
• T cell receptor
• CD8 T cells
• draining lymph node

Disclosure statement

The authors declare that they have no competing interests related to this work. However, S.D. has received compensation for consultant/advisory services from Lytix Biopharma, EMD Serono, Ono Pharmaceutical, Genentech, and Johnson & Johnson Enterprise Innovation Inc., and research support from Lytix Biopharma, Nanobiotix and Boehringer-Ingelheim for unrelated projects. S.C.F. is/has been holding research contracts with Merck, Varian, Bristol Myers Squibb, Celldex, Regeneron, Eisai, and Eli-Lilly, and has received consulting/advisory honoraria from Bayer, Bristol Myers Squibb, Varian, Elekta, Regeneron, Eisai, AstraZeneca, MedImmune, Merck US, EMD Serono, Accuray, Boehringer Ingelheim, Roche, Genentech, AstraZeneca, View Ray and Nanobiotix.

Additional information

Funding

This work was supported by NIH (R01CA198533 and R01CA201246), to S. Demaria, and BCRF-22-053 to S. Demaria and S.C. Formenti.