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

Ma, Y; Adjemian, S; Mattarollo, SR; Yamazaki, T; Aymeric, L; Yang, H; Portela Catani, JP; ... Kroemer, G; + view all (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(+)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.

Type: Article
Title: Anticancer chemotherapy-induced intratumoral recruitment and differentiation of antigen-presenting cells.
Location: United States
DOI: 10.1016/j.immuni.2013.03.003
Keywords: Adoptive Transfer, Animals, Anthracyclines, Antigen-Presenting Cells, Antigens, Ly, Antigens, Neoplasm, Antineoplastic Agents, Apoptosis, CD11b Antigen, CD11c Antigen, Cell Differentiation, Cell Line, Tumor, Cell Movement, Dendritic Cells, Granulocyte Precursor Cells, Immunity, Cellular, Mice, Mice, Inbred C57BL, Monocyte-Macrophage Precursor Cells, Neoplasms, Experimental, Nucleotidases, Receptors, Purinergic
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
URI: http://discovery.ucl.ac.uk/id/eprint/1395406
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