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

Jenna H. Newman, C. Brent Chesson, Nora L. Herzog, Praveen K. Bommareddy, Salvatore M. Aspromonte, Russell Pepe, Ricardo Estupinian, Mones M. Aboelatta, Stuti Buddhadev, Saeed Tarabichi, Michael Lee, Shengguo Li, Daniel J. Medina, Eileena F. Giurini, Kajal H. Gupta, Gabriel Guevara-Aleman, Marco Rossi, Christina Nowicki, Abdulkareem Abed, Josef W. GoldufskyJoseph R. Broucek, Raquel E. Redondo, David Rotter, Sachin R. Jhawar, Shang Jui Wang, Frederick J. Kohlhapp, Howard L. Kaufman, Paul G. Thomas, Vineet Gupta, Timothy M. Kuzel, Jochen Reiser, Joyce Paras, Michael P. Kane, Eric A. Singer, Jyoti Malhotra, Lisa K. Denzin, Derek B. Sant'Angelo, Arnold B. Rabson, Leonard Y. Lee, Ahmed Lasfar, John Langenfeld, Jason M. Schenkel, Mary Jo Fidler, Emily S. Ruiz, Amanda L. Marzo, Jai S. Rudra, Ann W. Silk, Andrew Zloza

Research output: Contribution to journalArticlepeer-review

125 Scopus citations

Abstract

Reprogramming the tumor microenvironment to increase immunemediated 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.

Original languageEnglish
Pages (from-to)1119-1128
Number of pages10
JournalProceedings of the National Academy of Sciences of the United States of America
Volume117
Issue number2
DOIs
StatePublished - Jan 14 2020

Keywords

  • Cancer
  • Flu shot
  • Influenza
  • Intratumoral
  • Vaccine

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