Blocking IL-1β reverses the immunosuppression in mouse breast cancer and synergizes with anti–PD-1 for tumor abrogation
Copyright policy )Blocking IL-1β reverses the immunosuppression in mouse breast cancer and synergizes with anti–PD-1 for tumor abrogation
SignificanceInflammation and immunosuppression are dominant features of cancer progression. In the tumor microenvironment, macrophages produce interleukin-1β (IL-1β), which subsequently recruits myeloid cells from the bone marrow. In mice deficient in IL-1β or in wild-type mice treated with anti–IL-1β Abs, implanted breast cancer tumors regress. Regression is due to decreased tumor-related immunosuppression, meditated mainly by macrophages, and increased antitumor immunity, mediated by elevated dendritic cell function and activated cytotoxic CD8 lymphocytes. Although anti–PD-1 reduces tumor growth, the combination of anti–IL-1β plus anti–PD-1 abrogated the tumors completely. These observations support clinical trials of blocking IL-1β in cancer and that anti–IL-1β is a checkpoint inhibitor.
- Radboud University Nijmegen Medical Centre Netherlands
- University of Colorado Boulder United States
- Ben-Gurion University of the Negev Israel
- Radboud University Nijmegen Netherlands
- University of Pittsburgh Medical Center United States
Radboudumc 4: lnfectious Diseases and Global Health RIMLS: Radboud Institute for Molecular Life Sciences, Immunosuppression Therapy, Inflammation, Mice, Inbred BALB C, CD11b Antigen, Macrophages, Interleukin-1beta, Radboud University Medical Center, Antibodies, Monoclonal, Antineoplastic Agents, Breast Neoplasms, Cell Differentiation, Dendritic Cells, CD8-Positive T-Lymphocytes, Granzymes, Interferon-gamma, Mice, Colony-Stimulating Factors, Cell Line, Tumor, Animals, Humans, Female, Internal Medicine - Radboud University Medical Center
Radboudumc 4: lnfectious Diseases and Global Health RIMLS: Radboud Institute for Molecular Life Sciences, Immunosuppression Therapy, Inflammation, Mice, Inbred BALB C, CD11b Antigen, Macrophages, Interleukin-1beta, Radboud University Medical Center, Antibodies, Monoclonal, Antineoplastic Agents, Breast Neoplasms, Cell Differentiation, Dendritic Cells, CD8-Positive T-Lymphocytes, Granzymes, Interferon-gamma, Mice, Colony-Stimulating Factors, Cell Line, Tumor, Animals, Humans, Female, Internal Medicine - Radboud University Medical Center
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