دورية أكاديمية
IL-1α Mediates Innate and Acquired Resistance to Immunotherapy in Melanoma.
| العنوان: | IL-1α Mediates Innate and Acquired Resistance to Immunotherapy in Melanoma. |
|---|---|
| المؤلفون: | Singh S; Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX 77054., Xiao Z; Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77054., Bavisi K; Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX 77054., Roszik J; Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77054., Melendez BD; Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77054., Wang Z; Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX 77054., Cantwell MJ; Memgen, Inc., Houston, TX 77046; and., Davis RE; Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX 77054., Lizee G; Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77054., Hwu P; Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77054., Neelapu SS; Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX 77054., Overwijk WW; Nektar Therapeutics, San Francisco, CA 94158., Singh M; Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX 77054; msingh4@mdanderson.org. |
| المصدر: | Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2021 Apr 15; Vol. 206 (8), pp. 1966-1975. Date of Electronic Publication: 2021 Mar 15. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S. |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association of Immunologists Country of Publication: United States NLM ID: 2985117R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1550-6606 (Electronic) Linking ISSN: 00221767 NLM ISO Abbreviation: J Immunol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Bethesda, MD : American Association of Immunologists Original Publication: Baltimore : Williams & Wilkins, c1950- |
| مواضيع طبية MeSH: | Drug Resistance, Neoplasm/*immunology , Immune Checkpoint Inhibitors/*therapeutic use , Immunotherapy/*methods , Interleukin-1alpha/*immunology , Melanoma, Experimental/*therapy, Animals ; Cell Line, Tumor ; Cytokines/immunology ; Cytokines/metabolism ; Humans ; Immune Checkpoint Inhibitors/immunology ; Interleukin-1alpha/metabolism ; Kaplan-Meier Estimate ; Melanoma, Experimental/immunology ; Mice, Inbred C57BL ; Myeloid-Derived Suppressor Cells/immunology ; Myeloid-Derived Suppressor Cells/metabolism ; Neutrophils/immunology ; Neutrophils/metabolism ; Signal Transduction/drug effects ; Signal Transduction/immunology ; Tumor Microenvironment/drug effects ; Tumor Microenvironment/immunology ; Mice |
| مستخلص: | Inflammation has long been associated with cancer initiation and progression; however, how inflammation causes immune suppression in the tumor microenvironment and resistance to immunotherapy is not well understood. In this study, we show that both innate proinflammatory cytokine IL-1α and immunotherapy-induced IL-1α make melanoma resistant to immunotherapy. In a mouse melanoma model, we found that tumor size was inversely correlated with response to immunotherapy. Large tumors had higher levels of IL-1α, Th2 cytokines, polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), and regulatory T cells but lower levels of IL-12, Th1 cytokines, and activated T cells. We found that therapy with adenovirus-encoded CD40L (rAd.CD40L) increased tumor levels of IL-1α and PMN-MDSCs. Blocking the IL-1 signaling pathway significantly decreased rAd.CD40L-induced PMN-MDSCs and their associated PD-L1 expression in the tumor microenvironment and enhanced tumor-specific immunity. Similarly, blocking the IL-1 signaling pathway improved the antimelanoma activity of anti-PD-L1 Ab therapy. Our study suggests that blocking the IL-1α signaling pathway may increase the efficacy of immunotherapies against melanoma. (Copyright © 2021 by The American Association of Immunologists, Inc.) |
| التعليقات: | Erratum in: J Immunol. 2024 Feb 1;212(3):500. (PMID: 38088809) |
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| معلومات مُعتمدة: | P30 CA016672 United States CA NCI NIH HHS; P50 CA093459 United States CA NCI NIH HHS; CA160521 Department of Defense |
| المشرفين على المادة: | 0 (Cytokines) 0 (Immune Checkpoint Inhibitors) 0 (Interleukin-1alpha) |
| تواريخ الأحداث: | Date Created: 20210316 Date Completed: 20210830 Latest Revision: 20240226 |
| رمز التحديث: | 20240226 |
| مُعرف محوري في PubMed: | PMC8023145 |
| DOI: | 10.4049/jimmunol.2000523 |
| PMID: | 33722878 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1550-6606 |
|---|---|
| DOI: | 10.4049/jimmunol.2000523 |