Title |
Targeting the IL1β Pathway for Cancer Immunotherapy Remodels the Tumor Microenvironment and Enhances Antitumor Immune Responses.
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Published in |
Cancer Immunology Research, April 2023
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DOI | 10.1158/2326-6066.cir-22-0290 |
Pubmed ID | |
Authors |
Rohan Diwanji, Neil A O'Brien, Jiyoung E Choi, Beverly Nguyen, Tyler Laszewski, Angelo L Grauel, Zheng Yan, Xin Xu, Jincheng Wu, David A Ruddy, Michelle Piquet, Marc R Pelletier, Alexander Savchenko, LaSalette Charette, Vanessa Rodrik-Outmezguine, Jason Baum, John M Millholland, Connie C Wong, Anne-Marie Martin, Glenn Dranoff, Iulian Pruteanu-Malinici, Viviana Cremasco, Catherine Sabatos-Peyton, Pushpa Jayaraman |
Abstract |
High levels of IL-1β can result in chronic inflammation, which in turn can promote tumor growth and metastasis. Inhibition of IL-1β could therefore be a promising therapeutic option in the treatment of cancer. Here, the effects of IL-1β blockade induced by the monoclonal antibodies canakinumab and gevokizumab were evaluated alone or in combination with docetaxel, anti-PD-1, anti-VEGFα and anti-TGFβ treatment in syngeneic and humanized mouse models of cancers of different origin. Canakinumab and gevokizumab did not show notable efficacy as single-agent therapies; however, IL-1β blockade enhanced the effectiveness of docetaxel and anti-PD-1. Accompanying these effects, blockade of IL-1β alone or in combination induced significant remodeling of the tumor microenvironment (TME), with decreased numbers of immune suppressive cells and increased tumor infiltration by dendritic cells and effector T cells. Further investigation revealed that cancer-associated fibroblasts (CAFs) were the cell type most affected by treatment with canakinumab or gevokizumab in terms of change in gene expression. IL-1β inhibition drove phenotypic changes in CAF populations, particularly those with the ability to influence immune cell recruitment. These results suggest that the observed remodeling of the TME following IL-1β blockade may stem from changes in CAF populations. Overall, the results presented here support the potential use of IL-1β inhibition in cancer treatment. Further exploration in ongoing clinical studies will help identify the best combination partners for different cancer types, cancer stages and lines of treatment. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 3 | 19% |
Mexico | 1 | 6% |
Switzerland | 1 | 6% |
United Kingdom | 1 | 6% |
Unknown | 10 | 63% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 9 | 56% |
Scientists | 5 | 31% |
Science communicators (journalists, bloggers, editors) | 2 | 13% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 7 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Other | 3 | 43% |
Researcher | 2 | 29% |
Student > Bachelor | 1 | 14% |
Unknown | 1 | 14% |
Readers by discipline | Count | As % |
---|---|---|
Immunology and Microbiology | 3 | 43% |
Biochemistry, Genetics and Molecular Biology | 1 | 14% |
Agricultural and Biological Sciences | 1 | 14% |
Nursing and Health Professions | 1 | 14% |
Unknown | 1 | 14% |