Intratumoral injection of the seasonal flu shot converts immunologically cold tumors to hot and serves as an immunotherapy for cancer
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Published:2019-12-30
Issue:2
Volume:117
Page:1119-1128
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ISSN:0027-8424
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Container-title:Proceedings of the National Academy of Sciences
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language:en
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Short-container-title:Proc Natl Acad Sci USA
Author:
Newman Jenna H., Chesson C. Brent, Herzog Nora L., Bommareddy Praveen K., Aspromonte Salvatore M., Pepe Russell, Estupinian Ricardo, Aboelatta Mones M., Buddhadev Stuti, Tarabichi Saeed, Lee Michael, Li Shengguo, Medina Daniel J., Giurini Eileena F., Gupta Kajal H., Guevara-Aleman Gabriel, Rossi Marco, Nowicki Christina, Abed Abdulkareem, Goldufsky Josef W., Broucek Joseph R., Redondo Raquel E., Rotter David, Jhawar Sachin R., Wang Shang-Jui, Kohlhapp Frederick J., Kaufman Howard L., Thomas Paul G.ORCID, Gupta Vineet, Kuzel Timothy M., Reiser Jochen, Paras Joyce, Kane Michael P., Singer Eric A., Malhotra Jyoti, Denzin Lisa K., Sant’Angelo Derek B., Rabson Arnold B., Lee Leonard Y., Lasfar Ahmed, Langenfeld John, Schenkel Jason M., Fidler Mary Jo, Ruiz Emily S., Marzo Amanda L., Rudra Jai S., Silk Ann W., Zloza Andrew
Abstract
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.
Publisher
Proceedings of the National Academy of Sciences
Subject
Multidisciplinary
Cited by
130 articles.
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