1. Anticancer Chemotherapy-Induced Intratumoral Recruitment and Differentiation of Antigen-Presenting Cells.
- Author
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Ma, Yuting, Adjemian, Sandy, Mattarollo, Stephen?R., Yamazaki, Takahiro, Aymeric, Laetitia, Yang, Heng, Portela?Catani, João?Paulo, Hannani, Dalil, Duret, Helene, Steegh, Kim, Martins, Isabelle, Schlemmer, Frederic, Michaud, Mickaël, Kepp, Oliver, Sukkurwala, Abdul?Qader, Menger, Laurie, Vacchelli, Erika, Droin, Nathalie, Galluzzi, Lorenzo, and Krzysiek, Roman
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ANTINEOPLASTIC agents , *CANCER chemotherapy , *CELL differentiation , *ANTIGEN presenting cells , *TREATMENT effectiveness , *CANCER cells , *ANTHRACYCLINES - Abstract
Summary: The therapeutic efficacy of anthracyclines relies on antitumor immune responses elicited by dying cancer cells. How chemotherapy-induced cell death leads to efficient antigen presentation to T cells, however, remains a conundrum. We found that intratumoral CD11c+CD11b+Ly6Chi cells, which displayed some characteristics of inflammatory dendritic cells and included granulomonocytic precursors, were crucial for anthracycline-induced anticancer immune responses. ATP released by dying cancer cells recruited myeloid cells into tumors and stimulated the local differentiation of CD11c+CD11b+Ly6Chi cells. Such cells efficiently engulfed tumor antigens in situ and presented them to T lymphocytes, thus vaccinating mice, upon adoptive transfer, against a challenge with cancer cells. Manipulations preventing tumor infiltration by CD11c+CD11b+Ly6Chi cells, such as the local overexpression of ectonucleotidases, the blockade of purinergic receptors, or the neutralization of CD11b, abolished the immune system-dependent antitumor activity of anthracyclines. Our results identify a subset of tumor-infiltrating leukocytes as therapy-relevant antigen-presenting cells. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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