Your browser doesn't support javascript.
loading
IL27 Signaling Serves as an Immunologic Checkpoint for Innate Cytotoxic Cells to Promote Hepatocellular Carcinoma.
Aghayev, Turan; Mazitova, Aleksandra M; Fang, Jennifer R; Peshkova, Iuliia O; Rausch, Matthew; Hung, Manhsin; White, Kerry F; Masia, Ricard; Titerina, Elizaveta K; Fatkhullina, Aliia R; Cousineau, Isabelle; Turcotte, Simon; Zhigarev, Dmitry; Marchenko, Anastasiia; Khoziainova, Svetlana; Makhov, Petr; Tan, Yin Fei; Kossenkov, Andrew V; Wiest, David L; Stagg, John; Wang, Xin Wei; Campbell, Kerry S; Dzutsev, Amiran K; Trinchieri, Giorgio; Hill, Jonathan A; Grivennikov, Sergei I; Koltsova, Ekaterina K.
Afiliación
  • Aghayev T; Blood Cell Development and Function Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
  • Mazitova AM; Blood Cell Development and Function Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
  • Fang JR; Cedars-Sinai Medical Center, Cedars-Sinai Cancer Institute, Department of Medicine, Department of Biomedical Sciences, Los Angeles, California.
  • Peshkova IO; Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
  • Rausch M; Blood Cell Development and Function Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
  • Hung M; Surface Oncology Inc., Cambridge, Massachusetts.
  • White KF; Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
  • Masia R; Liver Cancer Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
  • Titerina EK; Surface Oncology Inc., Cambridge, Massachusetts.
  • Fatkhullina AR; Surface Oncology Inc., Cambridge, Massachusetts.
  • Cousineau I; Blood Cell Development and Function Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
  • Turcotte S; Blood Cell Development and Function Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
  • Zhigarev D; Centre Hospitalier de l'Université de Montréal Research Center, Montreal, Quebec, Canada.
  • Marchenko A; Centre Hospitalier de l'Université de Montréal Research Center, Montreal, Quebec, Canada.
  • Khoziainova S; Blood Cell Development and Function Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
  • Makhov P; Cedars-Sinai Medical Center, Cedars-Sinai Cancer Institute, Department of Medicine, Department of Biomedical Sciences, Los Angeles, California.
  • Tan YF; Cedars-Sinai Medical Center, Cedars-Sinai Cancer Institute, Department of Medicine, Department of Biomedical Sciences, Los Angeles, California.
  • Kossenkov AV; Molecular Therapeutics Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
  • Wiest DL; Genomics Facility, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
  • Stagg J; Bioinformatics Facility, The Wistar Institute, Philadelphia, Pennsylvania.
  • Wang XW; Blood Cell Development and Function Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
  • Campbell KS; Centre Hospitalier de l'Université de Montréal Research Center, Montreal, Quebec, Canada.
  • Dzutsev AK; Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
  • Trinchieri G; Liver Cancer Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
  • Hill JA; Blood Cell Development and Function Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
  • Grivennikov SI; Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
  • Koltsova EK; Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
Cancer Discov ; 12(8): 1960-1983, 2022 08 05.
Article en En | MEDLINE | ID: mdl-35723626
Although inflammatory mechanisms driving hepatocellular carcinoma (HCC) have been proposed, the regulators of anticancer immunity in HCC remain poorly understood. We found that IL27 receptor (IL27R) signaling promotes HCC development in vivo. High IL27EBI3 cytokine or IL27RA expression correlated with poor prognosis for patients with HCC. Loss of IL27R suppressed HCC in vivo in two different models of hepatocarcinogenesis. Mechanistically, IL27R sig-naling within the tumor microenvironment restrains the cytotoxicity of innate cytotoxic lymphocytes. IL27R ablation enhanced their accumulation and activation, whereas depletion or functional impairment of innate cytotoxic cells abrogated the effect of IL27R disruption. Pharmacologic neutralization of IL27 signaling increased infiltration of innate cytotoxic lymphocytes with upregulated cytotoxic molecules and reduced HCC development. Our data reveal an unexpected role of IL27R signaling as an immunologic checkpoint regulating innate cytotoxic lymphocytes and promoting HCC of different etiologies, thus indicating a therapeutic potential for IL27 pathway blockade in HCC. SIGNIFICANCE: HCC, the most common form of liver cancer, is characterized by a poor survival rate and limited treatment options. The discovery of a novel IL27-dependent mechanism controlling anticancer cytotoxic immune response will pave the road for new treatment options for this devastating disease. This article is highlighted in the In This Issue feature, p. 1825.
Asunto(s)
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos T Citotóxicos / Carcinoma Hepatocelular / Interleucina-27 / Neoplasias Hepáticas / Antineoplásicos Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Cancer Discov Año: 2022 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos T Citotóxicos / Carcinoma Hepatocelular / Interleucina-27 / Neoplasias Hepáticas / Antineoplásicos Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Cancer Discov Año: 2022 Tipo del documento: Article Pais de publicación: Estados Unidos