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

Adjuvants, Immunologic / administration & dosage Animals B-Lymphocytes Basic-Leucine Zipper Transcription Factors / genetics CD8-Positive T-Lymphocytes / immunology Humans Immunity, Cellular Immunotherapy / methods Influenza A Virus, H1N1 Subtype / immunology Influenza Vaccines / administration & dosage Influenza, Human Injections, Intralesional Interleukin-10 Lung / pathology Lung Neoplasms / drug therapy Mice Mice, Inbred C57BL Neoplasms / drug therapy Repressor Proteins / genetics Seasons Skin Skin Neoplasms / drug therapy Squalene / administration & dosage Tumor Microenvironment / drug effects Vaccination
cancer flu shot influenza intratumoral vaccine

Journal

Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876

Informations de publication

Date de publication:
14 01 2020
Historique:
pubmed: 1 1 2020
medline: 16 4 2020
entrez: 1 1 2020
Statut: ppublish

Résumé

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

Identifiants

DOI: 10.1073/pnas.1904022116 PMID: 31888983 PMC: PMC6969546
pubmed: 31888983
pii: 1904022116
doi: 10.1073/pnas.1904022116
pmc: PMC6969546
doi:

Substances chimiques

Adjuvants, Immunologic 0
Basic-Leucine Zipper Transcription Factors 0
Influenza Vaccines 0
Repressor Proteins 0
SNFT protein, mouse 0
Interleukin-10 130068-27-8
Squalene 7QWM220FJH

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1119-1128

Subventions

Organisme : NIGMS NIH HHS
ID : R25 GM055145
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA225830
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008339
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA072720
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA225993
Pays : United States

Informations de copyright

Copyright © 2020 the Author(s). Published by PNAS.

Déclaration de conflit d'intérêts

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.

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Auteurs

Jenna H Newman (JH)

Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901.

C Brent Chesson (CB)

Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901.

Nora L Herzog (NL)

Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901.

Praveen K Bommareddy (PK)

Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901.

Salvatore M Aspromonte (SM)

Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901.

Russell 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.

Ricardo 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.

Mones M 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.

Stuti Buddhadev (S)

Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901.

Saeed Tarabichi (S)

Department of Surgery, Rutgers Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901.

Michael Lee (M)

Department of Surgery, Rutgers Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901.

Shengguo Li (S)

Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901.

Daniel J Medina (DJ)

Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901.

Eileena F Giurini (EF)

Department of Internal Medicine, Section of Hematology, Oncology, and Cell Therapy, Rush University Medical Center, Chicago, IL 60612.

Kajal H Gupta (KH)

Department of Internal Medicine, Section of Hematology, Oncology, and Cell Therapy, Rush University Medical Center, Chicago, IL 60612.

Gabriel Guevara-Aleman (G)

Department of Internal Medicine, Section of Hematology, Oncology, and Cell Therapy, Rush University Medical Center, Chicago, IL 60612.

Marco Rossi (M)

Department of Internal Medicine, Section of Hematology, Oncology, and Cell Therapy, Rush University Medical Center, Chicago, IL 60612.

Christina Nowicki (C)

Department of Internal Medicine, Section of Hematology, Oncology, and Cell Therapy, Rush University Medical Center, Chicago, IL 60612.

Abdulkareem Abed (A)

Department of Internal Medicine, Section of Hematology, Oncology, and Cell Therapy, Rush University Medical Center, Chicago, IL 60612.

Josef W Goldufsky (JW)

Department of Internal Medicine, Section of Hematology, Oncology, and Cell Therapy, Rush University Medical Center, Chicago, IL 60612.

Joseph R 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.

Raquel E 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.

David Rotter (D)

Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901.

Sachin R 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.

Shang-Jui Wang (SJ)

Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901.

Frederick J Kohlhapp (FJ)

Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901.

Howard L Kaufman (HL)

Division of Surgical Oncology, Massachusetts General Hospital, Boston, MA 02114.
Replimune, Inc., Woburn, MA 01801.

Paul G 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.
ORCID: 0000-0001-7955-0256

Vineet Gupta (V)

Department of Internal Medicine, Section of Hematology, Oncology, and Cell Therapy, Rush University Medical Center, Chicago, IL 60612.

Timothy M Kuzel (TM)

Department of Internal Medicine, Section of Hematology, Oncology, and Cell Therapy, Rush University Medical Center, Chicago, IL 60612.

Jochen Reiser (J)

Department of Internal Medicine, Section of Hematology, Oncology, and Cell Therapy, Rush University Medical Center, Chicago, IL 60612.

Joyce Paras (J)

Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901.

Michael P Kane (MP)

Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901.

Eric A 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.

Jyoti Malhotra (J)

Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901.

Lisa K Denzin (LK)

Child Health Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08901.

Derek B Sant'Angelo (DB)

Child Health Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08901.

Arnold B Rabson (AB)

Child Health Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08901.

Leonard Y Lee (LY)

Department of Surgery, Rutgers Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901.

Ahmed 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.

John Langenfeld (J)

Department of Surgery, Rutgers Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901.

Jason M 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.

Mary Jo Fidler (MJ)

Department of Internal Medicine, Section of Hematology, Oncology, and Cell Therapy, Rush University Medical Center, Chicago, IL 60612.

Emily S Ruiz (ES)

Department of Dermatology, Brigham and Women's Hospital, Boston, MA 02130.
Harvard Medical School, Boston, MA 02115.

Amanda L Marzo (AL)

Department of Internal Medicine, Section of Hematology, Oncology, and Cell Therapy, Rush University Medical Center, Chicago, IL 60612.

Jai S Rudra (JS)

Department of Biomedical Engineering, McKelvey School of Engineering, Washington University in Saint Louis, Saint Louis, MO 63105.

Ann W Silk (AW)

Harvard Medical School, Boston, MA 02115.
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215.

Andrew 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.

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Classifications MeSH

questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Effets physiologiques des médicaments › Facteurs immunologiques › Adjuvants immunologiques › Intratumoral injection of the seasonal flu...
questionsmedicales.fr › Eucaryotes › Animaux › Intratumoral injection of the seasonal flu...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes B › Intratumoral injection of the seasonal flu...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteurs de transcription à motif basique et à glissière à leucines › Intratumoral injection of the seasonal flu...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › Lymphocytes T CD8+ › Intratumoral injection of the seasonal flu...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Intratumoral injection of the seasonal flu...
questionsmedicales.fr › Phénomènes du système immunitaire › Immunité › Immunité acquise › Immunité cellulaire › Intratumoral injection of the seasonal flu...
questionsmedicales.fr › Thérapeutique › Biothérapie › Immunothérapie › Intratumoral injection of the seasonal flu...
questionsmedicales.fr › Virus › Virus à ARN › Virus à ARN de polarité négative › Orthomyxoviridae › Influenzavirus A › Virus de la grippe A › Sous-type H1N1 du virus de la grippe A › Intratumoral injection of the seasonal flu...
questionsmedicales.fr › Mélanges complexes › Produits biologiques › Vaccins › Vaccins antiviraux › Vaccins antigrippaux › Intratumoral injection of the seasonal flu...
questionsmedicales.fr › Maladies de l'appareil respiratoire › Infections de l'appareil respiratoire › Grippe humaine › Intratumoral injection of the seasonal flu...
questionsmedicales.fr › Thérapeutique › Traitement médicamenteux › Voies d'administration de substances chimiques et des médicaments › Injections › Injections intralésionnelles › Intratumoral injection of the seasonal flu...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Interleukines › Interleukine-10 › Intratumoral injection of the seasonal flu...
questionsmedicales.fr › Appareil respiratoire › Poumon › Intratumoral injection of the seasonal flu...
questionsmedicales.fr › Maladies de l'appareil respiratoire › Tumeurs de l'appareil respiratoire › Tumeurs du poumon › Intratumoral injection of the seasonal flu...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Intratumoral injection of the seasonal flu...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › Intratumoral injection of the seasonal flu...
questionsmedicales.fr › Tumeurs › Intratumoral injection of the seasonal flu...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Protéines de répression › Intratumoral injection of the seasonal flu...
questionsmedicales.fr › Environnement et santé publique › Environnement › Concepts météorologiques › Atmosphère › Climat › Saisons › Intratumoral injection of the seasonal flu...
questionsmedicales.fr › Système tégumentaire › Peau › Intratumoral injection of the seasonal flu...
questionsmedicales.fr › Maladies de la peau et du tissu conjonctif › Maladies de la peau › Tumeurs cutanées › Intratumoral injection of the seasonal flu...
questionsmedicales.fr › Composés chimiques organiques › Hydrocarbures › Terpènes › Triterpènes › Squalène › Intratumoral injection of the seasonal flu...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Microenvironnement cellulaire › Microenvironnement tumoral › Intratumoral injection of the seasonal flu...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Pratiques en santé publique › Prévention primaire › Immunisation › Vaccination › Intratumoral injection of the seasonal flu...