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

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.

• Authors: Yuting Ma, Sandy Adjemian, Stephen R Mattarollo, Takahiro Yamazaki, Laetitia Aymeric, Heng Yang, João Paulo Portela Catani, Dalil Hannani, Helene Duret, Kim Steegh, Isabelle Martins, Frederic Schlemmer, Mickaël Michaud, Oliver Kepp, Abdul Qader Sukkurwala, Laurie Menger, Erika Vacchelli, Nathalie Droin, Lorenzo Galluzzi, Roman Krzysiek, Siamon Gordon, Philip R Taylor, Peter Van Endert, Eric Solary, Mark J Smyth, Laurence Zitvogel, Guido Kroemer
• Journal: Immunity (Immunity) Vol. 38 Issue 4 Pg. 729-41 (Apr 18 2013) ISSN: 1097-4180 [Electronic] United States
• PMID: 23562161 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Anthracyclines
• Antigens, Ly
• Antigens, Neoplasm
• Antineoplastic Agents
• CD11b Antigen
• CD11c Antigen
• Ly-6C antigen, mouse
• Receptors, Purinergic
• Nucleotidases

Topics

• Adoptive Transfer
• Animals
• Anthracyclines (administration & dosage, adverse effects)
• Antigen-Presenting Cells (immunology)
• Antigens, Ly (metabolism)
• Antigens, Neoplasm (immunology)
• Antineoplastic Agents (administration & dosage, adverse effects)
• Apoptosis
• CD11b Antigen (metabolism)
• CD11c Antigen (metabolism)
• Cell Differentiation (drug effects)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Dendritic Cells (immunology)
• Granulocyte Precursor Cells (immunology)
• Immunity, Cellular
• Mice
• Mice, Inbred C57BL
• Monocyte-Macrophage Precursor Cells (immunology)
• Neoplasms, Experimental (drug therapy, immunology)
• Nucleotidases (metabolism)
• Receptors, Purinergic (metabolism)