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Interleukin-6 blockade abrogates immunotherapy toxicity and promotes tumor immunity.
Hailemichael, Yared; Johnson, Daniel H; Abdel-Wahab, Noha; Foo, Wai Chin; Bentebibel, Salah-Eddine; Daher, May; Haymaker, Cara; Wani, Khalida; Saberian, Chantal; Ogata, Dai; Kim, Sang T; Nurieva, Roza; Lazar, Alexander J; Abu-Sbeih, Hamzah; Fa'ak, Faisal; Mathew, Antony; Wang, Yinghong; Falohun, Adewunmi; Trinh, Van; Zobniw, Chrystia; Spillson, Christine; Burks, Jared K; Awiwi, Muhammad; Elsayes, Khaled; Soto, Luisa Solis; Melendez, Brenda D; Davies, Michael A; Wargo, Jennifer; Curry, Jonathan; Yee, Cassian; Lizee, Gregory; Singh, Shalini; Sharma, Padmanee; Allison, James P; Hwu, Patrick; Ekmekcioglu, Suhendan; Diab, Adi.
Afiliação
  • Hailemichael Y; Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Johnson DH; Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Precision Cancer Therapies Program, Department of Hematology and Medical Oncology, Ochsner Health, New Orleans, LA, USA.
  • Abdel-Wahab N; Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Section of Rheumatology & Clinical Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Rheumatology and Rehabilitation, Assiut University Hospi
  • Foo WC; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Bentebibel SE; Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Daher M; Department of Stem Cell Transplantation, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Haymaker C; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Wani K; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Saberian C; Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Ogata D; Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Kim ST; Section of Rheumatology & Clinical Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Nurieva R; Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences (GSBS), Houston, TX, USA.
  • Lazar AJ; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houst
  • Abu-Sbeih H; Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Fa'ak F; Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Mathew A; Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Wang Y; Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Falohun A; Section of Rheumatology & Clinical Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Trinh V; Pharmacy Clinical Programs, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Zobniw C; Pharmacy Clinical Programs, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Spillson C; Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Burks JK; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Awiwi M; Department of Abdominal Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Elsayes K; Department of Abdominal Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Soto LS; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Melendez BD; Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Davies MA; Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Wargo J; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX.
  • Curry J; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Yee C; Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Lizee G; Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Singh S; Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Sharma P; Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; The Immunotherapy Platform, The University of Texas MD Anderson Cancer Center, Houston, TX
  • Allison JP; Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; The Immunotherapy Platform, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Hwu P; Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Ekmekcioglu S; Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Diab A; Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: adiab@mdanderson.org.
Cancer Cell ; 40(5): 509-523.e6, 2022 05 09.
Article em En | MEDLINE | ID: mdl-35537412
Immune checkpoint blockade (ICB) therapy frequently induces immune-related adverse events. To elucidate the underlying immunobiology, we performed a deep immune analysis of intestinal, colitis, and tumor tissue from ICB-treated patients with parallel studies in preclinical models. Expression of interleukin-6 (IL-6), neutrophil, and chemotactic markers was higher in colitis than in normal intestinal tissue; T helper 17 (Th17) cells were more prevalent in immune-related enterocolitis (irEC) than T helper 1 (Th1). Anti-cytotoxic T-lymphocyte-associated antigen 4 (anti-CTLA-4) induced stronger Th17 memory in colitis than anti-program death 1 (anti-PD-1). In murine models, IL-6 blockade associated with improved tumor control and a higher density of CD4+/CD8+ effector T cells, with reduced Th17, macrophages, and myeloid cells. In an experimental autoimmune encephalomyelitis (EAE) model with tumors, combined IL-6 blockade and ICB enhanced tumor rejection while simultaneously mitigating EAE symptoms versus ICB alone. IL-6 blockade with ICB could de-couple autoimmunity from antitumor immunity.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Colite / Neoplasias Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Cancer Cell Assunto da revista: NEOPLASIAS Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Colite / Neoplasias Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Cancer Cell Assunto da revista: NEOPLASIAS Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos