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Anticancer chemotherapy-induced intratumoral recruitment and differentiation of antigen-presenting cells

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, Krzysiek, Roman, Gordon, Siamon, Taylor, Philip Russel, Van Endert, Peter, Solary, Eric, Smyth, Mark J., Zitvogel, Laurence and Kroemer, Guido 2013. Anticancer chemotherapy-induced intratumoral recruitment and differentiation of antigen-presenting cells. Immunity 38 (4) , pp. 729-741. 10.1016/j.immuni.2013.03.003

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Abstract

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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > R Medicine (General)
R Medicine > RZ Other systems of medicine
Uncontrolled Keywords: Adoptive Transfer;Animals;Anthracyclines;Antigen-Presenting Cells;Antigens CD11b;Antigens CD11c;Antigens Ly;Antigens Neoplasm;Antineoplastic Agents;Apoptosis;CellDifferentiation;Cell LineTumor;CellMovement;Dendritic Cells;GranulocytePrecursor Cells;Immunity Cellular;Mice;MiceInbredC57BL;Monocyte-Macrophage Precursor Cells;Neoplasms Experimental;Nucleotidases;Receptors Purinergic
Publisher: Elsevier
ISSN: 1074-7613
Last Modified: 04 Jun 2017 08:16
URI: http://orca-mwe.cf.ac.uk/id/eprint/75138

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