Abstract B015: Expansion and activation of CD103+ dendritic cell progenitors at the tumor site transform tumor response to PD-L1 and BRAF inhibition

Abstract

Abstract High numbers of melanoma lesions develop resistance to BRAF blockade or fail to respond to checkpoint inhibition therapy. Here we explored whether modulation of intratumoral antigen presenting cells (APCs) can help increase response to BRAF and checkpoint blockade in tamoxifen-induced Braf-mutant and B16 melanoma lesions. In both models, we found that CD103+ dendritic cells (DCs) were the only APCs that transported intact antigens to the lymph nodes and primed tumor-specific CD8+ T cells. CD103+ DC expressed high PD-L1 levels in the tumor and were required to promote anti-tumoral effects upon blockade of the checkpoint ligand PD-L1; however, PD-L1 inhibition only led to partial responses and minimal accumulation of intratumoral CD8+ T cells. Strikingly, systemic administration of fms-like tyrosine kinase 3 ligand (Flt3L) followed by intratumoral poly I:C injections expanded and activated CD103+ DC progenitors in the tumor, enhancing responses to BRAF and PD-L1 blockade and protecting mice from tumor rechallenge in a T cell dependent manner. Thus, the paucity of activated CD103+ DCs in tumors limits checkpoint blockade efficacy and Flt3L-poly I:C therapy can transform clinical responses to checkpoint and BRAF blockade. Salmon et al, 2016. Immunity, 44(4):924-38. Citation Format: Hélène Salmon, Juliana Idoyaga, Adeeb Rahman, Romain Remark, Sacha Gnjatic, Nina Bhardwaj, Joshua Brody, Anna Karolina Palucka, Florent Ginhoux, Miriam Merad. Expansion and activation of CD103+ dendritic cell progenitors at the tumor site transform tumor response to PD-L1 and BRAF inhibition [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr B015.