1. Anticancer chemotherapy-induced intratumoral recruitment and differentiation of antigen-presenting cells.
- Author
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Ma Y, Adjemian S, Mattarollo SR, Yamazaki T, Aymeric L, Yang H, Portela Catani JP, Hannani D, Duret H, Steegh K, Martins I, Schlemmer F, Michaud M, Kepp O, Sukkurwala AQ, Menger L, Vacchelli E, Droin N, Galluzzi L, Krzysiek R, Gordon S, Taylor PR, Van Endert P, Solary E, Smyth MJ, Zitvogel L, and Kroemer G
- Subjects
- Adoptive Transfer, Animals, Anthracyclines adverse effects, Antigens, Ly metabolism, Antigens, Neoplasm immunology, Antineoplastic Agents adverse effects, Apoptosis, CD11b Antigen metabolism, CD11c Antigen metabolism, Cell Differentiation drug effects, Cell Line, Tumor, Cell Movement drug effects, Granulocyte Precursor Cells immunology, Immunity, Cellular, Mice, Mice, Inbred C57BL, Monocyte-Macrophage Precursor Cells immunology, Neoplasms, Experimental drug therapy, Nucleotidases metabolism, Receptors, Purinergic metabolism, Anthracyclines administration & dosage, Antigen-Presenting Cells immunology, Antineoplastic Agents administration & dosage, Dendritic Cells immunology, Neoplasms, Experimental immunology
- 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(+)Ly6C(hi) 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(+)Ly6C(hi) 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(+)Ly6C(hi) 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., (Copyright © 2013 Elsevier Inc. All rights reserved.)
- Published
- 2013
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