title: IL-10 elicits IFNγ-dependent tumor immune surveillance.
abstract: Tumor immune surveillance and cancer immunotherapies are thought to depend on the intratumoral infiltration of activated CD8(+) T cells. Intratumoral CD8(+) T cells are rare and lack activity. IL-10 is thought to contribute to the underlying immune suppressive microenvironment. Defying those expectations we demonstrate that IL-10 induces several essential mechanisms for effective antitumor immune surveillance: infiltration and activation of intratumoral tumor-specific cytotoxic CD8(+) T cells, expression of the Th1 cytokine interferon-γ (IFNγ) and granzymes in CD8(+) T cells, and intratumoral antigen presentation molecules. Consequently, tumor immune surveillance is weakened in mice deficient for IL-10 whereas transgenic overexpression of IL-10 protects mice from carcinogenesis. Treatment with pegylated IL-10 restores tumor-specific intratumoral CD8(+) T cell function and controls tumor growth.
authors.affiliation: Merck Research Labs, Palo Alto, CA 94301, USA.
authors.forename: John B
authors.initials: JB
authors.lastname: Mumm
authors.forename: Jan
authors.initials: J
authors.lastname: Emmerich
authors.forename: Xueqing
authors.initials: X
authors.lastname: Zhang
authors.forename: Ivan
authors.initials: I
authors.lastname: Chan
authors.forename: Lingling
authors.initials: L
authors.lastname: Wu
authors.forename: Smita
authors.initials: S
authors.lastname: Mauze
authors.forename: Steven
authors.initials: S
authors.lastname: Blaisdell
authors.forename: Beth
authors.initials: B
authors.lastname: Basham
authors.forename: Jie
authors.initials: J
authors.lastname: Dai
authors.forename: Jeff
authors.initials: J
authors.lastname: Grein
authors.forename: Catherine
authors.initials: C
authors.lastname: Sheppard
authors.forename: Kyu
authors.initials: K
authors.lastname: Hong
authors.forename: Collette
authors.initials: C
authors.lastname: Cutler
authors.forename: Scott
authors.initials: S
authors.lastname: Turner
authors.forename: Drake
authors.initials: D
authors.lastname: LaFace
authors.forename: Melanie
authors.initials: M
authors.lastname: Kleinschek
authors.forename: Michael
authors.initials: M
authors.lastname: Judo
authors.forename: Gulesi
authors.initials: G
authors.lastname: Ayanoglu
authors.forename: John
authors.initials: J
authors.lastname: Langowski
authors.forename: Danling
authors.initials: D
authors.lastname: Gu
authors.forename: Brittany
authors.initials: B
authors.lastname: Paporello
authors.forename: Erin
authors.initials: E
authors.lastname: Murphy
authors.forename: Venkataraman
authors.initials: V
authors.lastname: Sriram
authors.forename: Saraswathi
authors.initials: S
authors.lastname: Naravula
authors.forename: Bela
authors.initials: B
authors.lastname: Desai
authors.forename: Satya
authors.initials: S
authors.lastname: Medicherla
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Seghezzi
authors.forename: Terrill
authors.initials: T
authors.lastname: McClanahan
authors.forename: Susan
authors.initials: S
authors.lastname: Cannon-Carlson
authors.forename: Amy M
authors.initials: AM
authors.lastname: Beebe
authors.forename: Martin
authors.initials: M
authors.lastname: Oft
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000201:enzymology / Q000378:metabolism; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D005260:Female; D053804:Granzymes / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D053709:Interleukin-10 Receptor alpha Subunit / Q000235:genetics / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D054353:Perforin / Q000378:metabolism; D012878:Skin Neoplasms / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D013154:Spleen / Q000378:metabolism; D014183:Transplantation, Heterologous; D047368:Tumor Burden; D019139:Tumor Escape
chemical_list: D000970:Antineoplastic Agents; C508609:IL10 protein, human; D053709:Interleukin-10 Receptor alpha Subunit; D054353:Perforin; D016753:Interleukin-10; D007371:Interferon-gamma; D053804:Granzymes; C509214:Gzmb protein, mouse