A high number of melanoma lesions develop resistance to BRAF blockade or fail to respond to checkpoint inhibition therapy. Here we explored whether modulation of intratumoral APC can increase responses to BRAF or PD-L1 blockade in Braf-mutant and B16 melanoma. In both models, CD103+ DC were the only APC that transported intact antigens to the lymph nodes and primed tumor-specific CD8+ T cells. CD103+ DC expressed high PD-L1 levels, however PD-L1 or BRAF blockade led to partial response and minimal accumulation of intratumoral T cells. Strikingly, systemic Flt3L followed by intratumoral poly I:C injections expanded and activated CD103+ DC progenitors in the tumor mass, leading to dramatic expansion of intratumoral CD8+ T cells enhancing responses to BRAF and PD-L1 blockade and protecting mice from tumor rechallenge. Thus the paucity of activated CD103+ DC in tumors limit checkpoint blockade efficacy and Flt3L/poly I:C combination can significantly enhance clinical response to checkpoint and BRAF blockade.
Citation Format: Hélène Salmon, Juliana Idoyaga, Adeeb Rahman, Anna Karolina Palucka, Nina Bhardwaj, Florent Ginhoux, Miriam Merad. Expansion and activation of CD103+ DC progenitors at the tumor site promote T cell accumulation in melanoma lesions and transform clinical response to BRAF and PD-L1 blockade. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr B058.
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