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Merck

Interleukin-6 blockade abrogates immunotherapy toxicity and promotes tumor immunity.

Cancer cell (2022-05-11)
Yared Hailemichael, Daniel H Johnson, Noha Abdel-Wahab, Wai Chin Foo, Salah-Eddine Bentebibel, May Daher, Cara Haymaker, Khalida Wani, Chantal Saberian, Dai Ogata, Sang T Kim, Roza Nurieva, Alexander J Lazar, Hamzah Abu-Sbeih, Faisal Fa'ak, Antony Mathew, Yinghong Wang, Adewunmi Falohun, Van Trinh, Chrystia Zobniw, Christine Spillson, Jared K Burks, Muhammad Awiwi, Khaled Elsayes, Luisa Solis Soto, Brenda D Melendez, Michael A Davies, Jennifer Wargo, Jonathan Curry, Cassian Yee, Gregory Lizee, Shalini Singh, Padmanee Sharma, James P Allison, Patrick Hwu, Suhendan Ekmekcioglu, Adi Diab
ABSTRACT

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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Sigma-Aldrich
Anticorpo anti-ROR gamma T, clone 6F3.1, clone 6F3.1, from mouse