학술논문
Enhancing cancer immunotherapy via inhibition of soluble epoxide hydrolase.
Document Type
Academic Journal
Author
Kelly AG; Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215.; Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215.; Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215.; Wang W; Department of Entomology and Nematology, University of California, Davis, CA 95616.; University of California Davis Comprehensive Cancer Center, Sacramento, CA 95817.; Department of Food Science, Purdue University, West Lafayette, IN 47907.; Rothenberger E; Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215.; Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215.; Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215.; Yang J; Department of Entomology and Nematology, University of California, Davis, CA 95616.; University of California Davis Comprehensive Cancer Center, Sacramento, CA 95817.; Gilligan MM; Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215.; Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215.; Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215.; Kipper FC; Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215.; Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215.; Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215.; Attaya A; Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215.; Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215.; Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215.; Gartung A; Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215.; Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215.; Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215.; Hwang SH; Department of Entomology and Nematology, University of California, Davis, CA 95616.; University of California Davis Comprehensive Cancer Center, Sacramento, CA 95817.; Gillespie MJ; Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215.; Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215.; Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215.; Bayer RL; Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215.; Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215.; Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215.; Quinlivan KM; Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215.; Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215.; Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215.; Torres KL; Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215.; Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215.; Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215.; Huang S; Institute of Systems Biology, Seattle, WA 98109.; Mitsiades N; University of California Davis Comprehensive Cancer Center, Sacramento, CA 95817.; Department of Internal Medicine, University of California Davis, CA 95817.; Yang H; Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215.; Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215.; Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215.; Department of Food Nutrition and Safety, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China.; Hammock BD; Department of Entomology and Nematology, University of California, Davis, CA 95616.; University of California Davis Comprehensive Cancer Center, Sacramento, CA 95817.; Panigrahy D; Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215.; Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215.; Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215.
Source
Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE
Subject
Language
English
Abstract
Cancer therapy, including immunotherapy, is inherently limited by chronic inflammation-induced tumorigenesis and toxicity within the tumor microenvironment. Thus, stimulating the resolution of inflammation may enhance immunotherapy and improve the toxicity of immune checkpoint inhibition (ICI). As epoxy-fatty acids (EpFAs) are degraded by the enzyme soluble epoxide hydrolase (sEH), the inhibition of sEH increases endogenous EpFA levels to promote the resolution of cancer-associated inflammation. Here, we demonstrate that systemic treatment with ICI induces sEH expression in multiple murine cancer models. Dietary omega-3 polyunsaturated fatty acid supplementation and pharmacologic sEH inhibition, both alone and in combination, significantly enhance anti-tumor activity of ICI in these models. Notably, pharmacological abrogation of the sEH pathway alone or in combination with ICI counter-regulates an ICI-induced pro-inflammatory and pro-tumorigenic cytokine storm. Thus, modulating endogenous EpFA levels through dietary supplementation or sEH inhibition may represent a unique strategy to enhance the anti-tumor activity of paradigm cancer therapies.
Competing Interests: Competing interests statement:J.Y., S.H.H., and B.D.H. are affiliated with EicOsis Human Health which has a sEH inhibitor in human 1b safety trials. J.Y., S.H.H., and B.D.H. have stock options in EicOsis Human Health to disclose. The authors disclose the following patent filing: E.R., S.H.H., B.D.H., and D.P. Methods of Improving Cancer Immunotherapy. Provisional Application No. 63/326,504 filed April 1, 2022. Use of dual COX-2/sEH inhibitors with immunotherapy Use of dual COX-2/sEH inhibitors with immunotherapy. D.P. has received consulting fees from attorneys representing plaintiffs in cases involving exposure to chemical agents. The other authors declare they have no actual or potential competing financial interests.
Competing Interests: Competing interests statement:J.Y., S.H.H., and B.D.H. are affiliated with EicOsis Human Health which has a sEH inhibitor in human 1b safety trials. J.Y., S.H.H., and B.D.H. have stock options in EicOsis Human Health to disclose. The authors disclose the following patent filing: E.R., S.H.H., B.D.H., and D.P. Methods of Improving Cancer Immunotherapy. Provisional Application No. 63/326,504 filed April 1, 2022. Use of dual COX-2/sEH inhibitors with immunotherapy Use of dual COX-2/sEH inhibitors with immunotherapy. D.P. has received consulting fees from attorneys representing plaintiffs in cases involving exposure to chemical agents. The other authors declare they have no actual or potential competing financial interests.