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


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.

SUBMITTER: Newman JH 

PROVIDER: S-EPMC6969546 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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

Newman Jenna H JH   Chesson C Brent CB   Herzog Nora L NL   Bommareddy Praveen K PK   Aspromonte Salvatore M SM   Pepe Russell R   Estupinian Ricardo R   Aboelatta Mones M MM   Buddhadev Stuti S   Tarabichi Saeed S   Lee Michael M   Li Shengguo S   Medina Daniel J DJ   Giurini Eileena F EF   Gupta Kajal H KH   Guevara-Aleman Gabriel G   Rossi Marco M   Nowicki Christina C   Abed Abdulkareem A   Goldufsky Josef W JW   Broucek Joseph R JR   Redondo Raquel E RE   Rotter David D   Jhawar Sachin R SR   Wang Shang-Jui SJ   Kohlhapp Frederick J FJ   Kaufman Howard L HL   Thomas Paul G PG   Gupta Vineet V   Kuzel Timothy M TM   Reiser Jochen J   Paras Joyce J   Kane Michael P MP   Singer Eric A EA   Malhotra Jyoti J   Denzin Lisa K LK   Sant'Angelo Derek B DB   Rabson Arnold B AB   Lee Leonard Y LY   Lasfar Ahmed A   Langenfeld John J   Schenkel Jason M JM   Fidler Mary Jo MJ   Ruiz Emily S ES   Marzo Amanda L AL   Rudra Jai S JS   Silk Ann W AW   Zloza Andrew A  

Proceedings of the National Academy of Sciences of the United States of America 20191230 2


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  ...[more]

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