Intratumoral injection of the seasonal flu shot converts immunologically cold tumors to hot and serves as an immunotherapy for cancer.

Autor:	Newman JH; Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901., Chesson CB; Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901., Herzog NL; Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901., Bommareddy PK; Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901., Aspromonte SM; Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901., Pepe R; Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901.; Department of Surgery, Rutgers Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901., Estupinian R; Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901.; Department of Internal Medicine, Section of Hematology, Oncology, and Cell Therapy, Rush University Medical Center, Chicago, IL 60612., Aboelatta MM; Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901.; Institute for Genomic Medicine, Columbia University Irving Medical Center, New York, NY 10032., Buddhadev S; Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901., Tarabichi S; Department of Surgery, Rutgers Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901., Lee M; Department of Surgery, Rutgers Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901., Li S; Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901., Medina DJ; Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901., Giurini EF; Department of Internal Medicine, Section of Hematology, Oncology, and Cell Therapy, Rush University Medical Center, Chicago, IL 60612., Gupta KH; Department of Internal Medicine, Section of Hematology, Oncology, and Cell Therapy, Rush University Medical Center, Chicago, IL 60612., Guevara-Aleman G; Department of Internal Medicine, Section of Hematology, Oncology, and Cell Therapy, Rush University Medical Center, Chicago, IL 60612., Rossi M; Department of Internal Medicine, Section of Hematology, Oncology, and Cell Therapy, Rush University Medical Center, Chicago, IL 60612., Nowicki C; Department of Internal Medicine, Section of Hematology, Oncology, and Cell Therapy, Rush University Medical Center, Chicago, IL 60612., Abed A; Department of Internal Medicine, Section of Hematology, Oncology, and Cell Therapy, Rush University Medical Center, Chicago, IL 60612., Goldufsky JW; Department of Internal Medicine, Section of Hematology, Oncology, and Cell Therapy, Rush University Medical Center, Chicago, IL 60612., Broucek JR; Department of Internal Medicine, Section of Hematology, Oncology, and Cell Therapy, Rush University Medical Center, Chicago, IL 60612.; Department of Surgery, Vanderbilt University Medical Center, Nashville, TN 37232., Redondo RE; Department of Internal Medicine, Section of Hematology, Oncology, and Cell Therapy, Rush University Medical Center, Chicago, IL 60612.; Department of Surgery, Franciscan Health, Munster, IN 46321., Rotter D; Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901., Jhawar SR; Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901.; Department of Radiation Oncology, Arthur G. James Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210., Wang SJ; Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901., Kohlhapp FJ; Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901., Kaufman HL; Division of Surgical Oncology, Massachusetts General Hospital, Boston, MA 02114.; Replimune, Inc., Woburn, MA 01801., Thomas PG; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105.; Integrated Biomedical Sciences Program, University of Tennessee Health Science Center, Memphis, TN 38105., Gupta V; Department of Internal Medicine, Section of Hematology, Oncology, and Cell Therapy, Rush University Medical Center, Chicago, IL 60612., Kuzel TM; Department of Internal Medicine, Section of Hematology, Oncology, and Cell Therapy, Rush University Medical Center, Chicago, IL 60612., Reiser J; Department of Internal Medicine, Section of Hematology, Oncology, and Cell Therapy, Rush University Medical Center, Chicago, IL 60612., Paras J; Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901., Kane MP; Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901., Singer EA; Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901.; Department of Surgery, Rutgers Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901., Malhotra J; Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901., Denzin LK; Child Health Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08901., Sant'Angelo DB; Child Health Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08901., Rabson AB; Child Health Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08901., Lee LY; Department of Surgery, Rutgers Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901., Lasfar A; Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901.; Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854., Langenfeld J; Department of Surgery, Rutgers Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901., Schenkel JM; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.; Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115., Fidler MJ; Department of Internal Medicine, Section of Hematology, Oncology, and Cell Therapy, Rush University Medical Center, Chicago, IL 60612., Ruiz ES; Department of Dermatology, Brigham and Women's Hospital, Boston, MA 02130.; Harvard Medical School, Boston, MA 02115., Marzo AL; Department of Internal Medicine, Section of Hematology, Oncology, and Cell Therapy, Rush University Medical Center, Chicago, IL 60612., Rudra JS; Department of Biomedical Engineering, McKelvey School of Engineering, Washington University in Saint Louis, Saint Louis, MO 63105., Silk AW; Harvard Medical School, Boston, MA 02115.; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215., Zloza A; Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901; Andrew_Zloza@rush.edu.; Department of Surgery, Rutgers Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901.; Department of Internal Medicine, Section of Hematology, Oncology, and Cell Therapy, Rush University Medical Center, Chicago, IL 60612.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2020 Jan 14; Vol. 117 (2), pp. 1119-1128. Date of Electronic Publication: 2019 Dec 30.
DOI:	10.1073/pnas.1904022116
Abstrakt:	Reprogramming the tumor microenvironment to increase immune-mediated responses is currently of intense interest. Patients with immune-infiltrated "hot" tumors demonstrate higher treatment response rates and improved survival. However, only the minority of tumors are hot, and a limited proportion of patients benefit from immunotherapies. Innovative approaches that make tumors hot can have immediate impact particularly if they repurpose drugs with additional cancer-unrelated benefits. The seasonal influenza vaccine is recommended for all persons over 6 mo without prohibitive contraindications, including most cancer patients. Here, we report that unadjuvanted seasonal influenza vaccination via intratumoral, but not intramuscular, injection converts "cold" tumors to hot, generates systemic CD8 + T cell-mediated antitumor immunity, and sensitizes resistant tumors to checkpoint blockade. Importantly, intratumoral vaccination also provides protection against subsequent active influenza virus lung infection. Surprisingly, a squalene-based adjuvanted vaccine maintains intratumoral regulatory B cells and fails to improve antitumor responses, even while protecting against active influenza virus lung infection. Adjuvant removal, B cell depletion, or IL-10 blockade recovers its antitumor effectiveness. Our findings propose that antipathogen vaccines may be utilized for both infection prevention and repurposing as a cancer immunotherapy. Competing Interests: Competing interest statement: P.K.B. and H.L.K. are employees of Replimune, Inc. E.A.S. receives research funding from Astellas/Medivation. M.J.F receives research funding from Pfizer and Biodesix, consulting funds from Astrazeneca and Pfizer, and honoraria from AstraZeneca, Merck, and Genentech. All other authors declare no conflicts of interest. (Copyright © 2020 the Author(s). Published by PNAS.)
Databáze:	MEDLINE
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