title: Adoptively transferred immune T cells eradicate established tumors despite cancer-induced immune suppression.
abstract: Myeloid-derived CD11b(+)Gr1(+) suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) are considered a major obstacle for effective adoptive T cell therapy. Myeloid cells suppress naive T cell proliferation ex vivo and can prevent the generation of T cell responses in vivo. We find, however, that adoptively transferred immune T cells eradicate well-established tumors in the presence of MDSCs and TAMs, which are strongly immunosuppressive ex vivo. These MDSCs and TAMs were comparable in numbers and immunosuppressive capacity among different tumor models. Longitudinal microscopy of tumors in vivo revealed that after T cell transfer, tumor vasculature and cancer cells disappeared simultaneously. During T cell-mediated tumor destruction, the tumor stroma contained abundant myeloid cells (mainly TAMs) that retained their suppressive properties. Preimmunized but not naive mice resisted immune suppression caused by an unrelated tumor burden, supporting the idea that in vivo, myeloid immunosuppressive cells can suppress naive but not memory T cell responses.
authors.affiliation: Department of Pathology, University of Chicago, Chicago, IL 60637.
authors.forename: Ainhoa
authors.initials: A
authors.lastname: Arina
authors.forename: Karin
authors.initials: K
authors.lastname: Schreiber
authors.forename: David C
authors.initials: DC
authors.lastname: Binder
authors.forename: Theodore G
authors.initials: TG
authors.lastname: Karrison
authors.forename: Rebecca B
authors.initials: RB
authors.lastname: Liu
authors.forename: Hans
authors.initials: H
authors.lastname: Schreiber
mesh_terms: D000818:Animals; D039481:CD11b Antigen / Q000032:analysis; D019496:Cancer Vaccines / Q000276:immunology; D004268:DNA-Binding Proteins / Q000172:deficiency; D018398:Homeodomain Proteins / Q000235:genetics; D007114:Immunization; D007156:Immunologic Memory; D016219:Immunotherapy, Adoptive; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D022423:Myeloid Cells / Q000276:immunology*; D009374:Neoplasms, Experimental / Q000098:blood supply / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D009389:Neovascularization, Pathologic / Q000276:immunology / Q000628:therapy; D019707:Receptors, Chemokine / Q000032:analysis; D012884:Skin Window Technique; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000637:transplantation*; D047368:Tumor Burden; D019139:Tumor Escape / Q000276:immunology*
chemical_list: D039481:CD11b Antigen; D019496:Cancer Vaccines; D004268:DNA-Binding Proteins; C503133:Gr-1 protein, mouse; D018398:Homeodomain Proteins; C499308:Rag2 protein, mouse; D019707:Receptors, Chemokine; C064658:RAG-1 protein