Title
Expansion and Activation of CD103(+) Dendritic Cell Progenitors at the Tumor Site Enhances Tumor Responses to Therapeutic PD-L1 and BRAF Inhibition.
Document Type
Article
Publication Date
4-19-2016
JAX Source
Immunity 2016 Apr 19; 44(4):924-38.
Volume
44
Issue
4
First Page
924
Last Page
938
ISSN
1097-4180
PMID
27096321
Abstract
Large numbers of melanoma lesions develop resistance to targeted inhibition of mutant BRAF or fail to respond to checkpoint blockade. We explored whether modulation of intratumoral antigen-presenting cells (APCs) could increase responses to these therapies. Using mouse melanoma models, we found that CD103(+) dendritic cells (DCs) were the only APCs transporting intact antigens to the lymph nodes and priming tumor-specific CD8(+) T cells. CD103(+) DCs were required to promote anti-tumoral effects upon blockade of the checkpoint ligand PD-L1; however, PD-L1 inhibition only led to partial responses. Systemic administration of the growth factor 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. Thus, the paucity of activated CD103(+) DCs in tumors limits checkpoint-blockade efficacy and combined FLT3L and poly I:C therapy can enhance tumor responses to checkpoint and BRAF blockade. Immunity 2016 Apr 19; 44(4):924-38.
Recommended Citation
Salmon H,
Idoyaga J,
Rahman A,
Leboeuf M,
Remark R,
Jordan S,
Casanova-Acebes M,
Khudoynazarova M,
Agudo J,
Tung N,
Chakarov S,
Rivera C,
Hogstad B,
Bosenberg M,
Hashimoto D,
Gnjatic S,
Bhardwaj N,
Palucka K,
Brown B,
Brody J,
Ginhoux F,
Merad M.
Expansion and Activation of CD103(+) Dendritic Cell Progenitors at the Tumor Site Enhances Tumor Responses to Therapeutic PD-L1 and BRAF Inhibition. Immunity 2016 Apr 19; 44(4):924-38.