Targeting DDR2 enhances tumor response to anti–PD-1 immunotherapy
Menée in vitro et à l'aide de modèles murins de tumeurs (vessie, sein, côlon, sarcome et mélanome), cette étude met en évidence l'intérêt de cibler les récepteurs DDR2 pour augmenter la réponse tumorale aux immunothérapies anti-PD-1
While a fraction of cancer patients treated with anti–PD-1 show durable therapeutic responses, most remain unresponsive, highlighting the need to better understand and improve these therapies. Using an in vivo screening approach with a customized shRNA pooled library, we identified DDR2 as a leading target for the enhancement of response to anti–PD-1 immunotherapy. Using isogenic in vivo murine models across five different tumor histologies—bladder, breast, colon, sarcoma, and melanoma—we show that DDR2 depletion increases sensitivity to anti–PD-1 treatment compared to monotherapy. Combination treatment of tumor-bearing mice with anti–PD-1 and dasatinib, a tyrosine kinase inhibitor of DDR2, led to tumor load reduction. RNA-seq and CyTOF analysis revealed higher CD8+ T cell populations in tumors with DDR2 depletion and those treated with dasatinib when either was combined with anti–PD-1 treatment. Our work provides strong scientific rationale for targeting DDR2 in combination with PD-1 inhibitors.
Science Advances 2019