Faculty, Staff and Student Publications
Publication Date
5-9-2022
Journal
Cancer Cell
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.
Trial registration: ClinicalTrials.gov NCT04940299.
Keywords
Animals, Colitis, Humans, Immunologic Factors, Immunotherapy, Interleukin-6, Mice, Myeloid Cells, Neoplasms, Immunity, Toxicity, Colitis, Arthritis, Immune checkpoint blockade, Interleukin-6, Melanoma, Th17 memory, TC1/TC17, Th1/Th17, EAE
DOI
10.1016/j.ccell.2022.04.004
PMID
35537412
PMCID
PMC9221568
PubMedCentral® Posted Date
5-9-2023
PubMedCentral® Full Text Version
Author MSS
Graphical Abstract
Published Open-Access
yes
Included in
Bioinformatics Commons, Biological Phenomena, Cell Phenomena, and Immunity Commons, Biomedical Informatics Commons, Oncology Commons
