title: 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.affiliation: Institut National de la Santé et de la Recherche Médicale, Villejuif, France.
authors.forename: Yuting
authors.initials: Y
authors.lastname: Ma
authors.forename: Sandy
authors.initials: S
authors.lastname: Adjemian
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Mattarollo
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yamazaki
authors.forename: Laetitia
authors.initials: L
authors.lastname: Aymeric
authors.forename: Heng
authors.initials: H
authors.lastname: Yang
authors.forename: João Paulo
authors.initials: JP
authors.lastname: Portela Catani
authors.forename: Dalil
authors.initials: D
authors.lastname: Hannani
authors.forename: Helene
authors.initials: H
authors.lastname: Duret
authors.forename: Kim
authors.initials: K
authors.lastname: Steegh
authors.forename: Isabelle
authors.initials: I
authors.lastname: Martins
authors.forename: Frederic
authors.initials: F
authors.lastname: Schlemmer
authors.forename: Mickaël
authors.initials: M
authors.lastname: Michaud
authors.forename: Oliver
authors.initials: O
authors.lastname: Kepp
authors.forename: Abdul Qader
authors.initials: AQ
authors.lastname: Sukkurwala
authors.forename: Laurie
authors.initials: L
authors.lastname: Menger
authors.forename: Erika
authors.initials: E
authors.lastname: Vacchelli
authors.forename: Nathalie
authors.initials: N
authors.lastname: Droin
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Galluzzi
authors.forename: Roman
authors.initials: R
authors.lastname: Krzysiek
authors.forename: Siamon
authors.initials: S
authors.lastname: Gordon
authors.forename: Philip R
authors.initials: PR
authors.lastname: Taylor
authors.forename: Peter
authors.initials: P
authors.lastname: Van Endert
authors.forename: Eric
authors.initials: E
authors.lastname: Solary
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Smyth
authors.forename: Laurence
authors.initials: L
authors.lastname: Zitvogel
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D018943:Anthracyclines / Q000008:administration & dosage* / Q000009:adverse effects; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000950:Antigens, Ly / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000276:immunology; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D017209:Apoptosis; D039481:CD11b Antigen / Q000378:metabolism; D039521:CD11c Antigen / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D003713:Dendritic Cells / Q000276:immunology*; D042381:Granulocyte Precursor Cells / Q000276:immunology; D007111:Immunity, Cellular; D051379:Mice; D008810:Mice, Inbred C57BL; D055017:Monocyte-Macrophage Precursor Cells / Q000276:immunology; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000276:immunology*; D009708:Nucleotidases / Q000378:metabolism; D011983:Receptors, Purinergic / Q000378:metabolism
chemical_list: D018943:Anthracyclines; D000950:Antigens, Ly; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D039481:CD11b Antigen; D039521:CD11c Antigen; C494192:Ly-6C antigen, mouse; D011983:Receptors, Purinergic; D009708:Nucleotidases