title: CCL2/CCR2-dependent recruitment of functional antigen-presenting cells into tumors upon chemotherapy.
abstract: The therapeutic efficacy of anthracyclines relies, at least partially, on the induction of a dendritic cell- and T-lymphocyte-dependent anticancer immune response. Here, we show that anthracycline-based chemotherapy promotes the recruitment of functional CD11b(+)CD11c(+)Ly6C(high)Ly6G(-)MHCII(+) dendritic cell-like antigen-presenting cells (APC) into the tumor bed, but not into lymphoid organs. Accordingly, draining lymph nodes turned out to be dispensable for the proliferation of tumor antigen-specific T cells within neoplastic lesions as induced by anthracyclines. In addition, we found that tumors treated with anthracyclines manifest increased expression levels of the chemokine Ccl2. Such a response is important as neoplasms growing in Ccl2(-/-) mice failed to accumulate dendritic cell-like APCs in response to chemotherapy. Moreover, cancers developing in mice lacking Ccl2 or its receptor (Ccr2) exhibited suboptimal therapeutic responses to anthracycline-based chemotherapy. Altogether, our results underscore the importance of the CCL2/CCR2 signaling axis for therapeutic anticancer immune responses as elicited by immunogenic chemotherapy.
authors.affiliation: Authors' Affiliations: INSERM, U848; Institut Gustave Roussy; INSERM, U1015, CBT1017; Metabolomics and Cell Biology Platforms, Institut Gustave Roussy, Villejuif, France; Université Paris Descartes/Paris V, Sorbonne Paris Cité; Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, Paris; Université Paris Sud/Paris XI; Le Kremlin Bicêtre; Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP; Paris; INSERM, UMR 996, LabEx LERMIT, Clamart, France; Cancer Immunology Program, Peter MacCallum Cancer Centre, East Melbourne, Victoria; Diamantina Institute; School of Medicine, University of Queensland; Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute; Cancer Immunoregulation and Immunotherapy Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia; Laboratorio de Vetores Virais, Instituto do Coração, FM-USP, São Paulo, Brazil; and Genomics & Immunoregulation, LIMES-Institute, University of Bonn, Bonn, Germany.
authors.forename: Yuting
authors.initials: Y
authors.lastname: Ma
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Mattarollo
authors.forename: Sandy
authors.initials: S
authors.lastname: Adjemian
authors.forename: Heng
authors.initials: H
authors.lastname: Yang
authors.forename: Laetitia
authors.initials: L
authors.lastname: Aymeric
authors.forename: Dalil
authors.initials: D
authors.lastname: Hannani
authors.forename: João Paulo
authors.initials: JP
authors.lastname: Portela Catani
authors.forename: Helene
authors.initials: H
authors.lastname: Duret
authors.forename: Michele W L
authors.initials: MW
authors.lastname: Teng
authors.forename: Oliver
authors.initials: O
authors.lastname: Kepp
authors.forename: Yidan
authors.initials: Y
authors.lastname: Wang
authors.forename: Antonella
authors.initials: A
authors.lastname: Sistigu
authors.forename: Joachim L
authors.initials: JL
authors.lastname: Schultze
authors.forename: Gautier
authors.initials: G
authors.lastname: Stoll
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Galluzzi
authors.forename: Laurence
authors.initials: L
authors.lastname: Zitvogel
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Smyth
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
mesh_terms: D000818:Animals; D018943:Anthracyclines / Q000627:therapeutic use; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000378:metabolism; D000970:Antineoplastic Agents / Q000627:therapeutic use; D045744:Cell Line, Tumor; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology; D005260:Female; D005434:Flow Cytometry; D008197:Lymph Node Excision; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy*; D020411:Oligonucleotide Array Sequence Analysis; D054390:Receptors, CCR2 / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology
chemical_list: D018943:Anthracyclines; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; C491768:Ccl2 protein, mouse; C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D054390:Receptors, CCR2