دورية أكاديمية

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

التفاصيل البيبلوغرافية
العنوان: Intratumoral injection of the seasonal flu shot converts immunologically cold tumors to hot and serves as an immunotherapy for cancer.
المؤلفون: 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, Shengguo Li, Medina, Daniel J., Giurini, Eileena F., Gupta, Kajal H., Guevara-Aleman, Gabriel, Rossi, Marco, Nowicki, Christina, Abed, Abdulkareem, Goldufsky, Josef W.
المصدر: Proceedings of the National Academy of Sciences of the United States of America; 1/14/2020, Vol. 117 Issue 2, p1119-1128, 10p
مصطلحات موضوعية: INFLUENZA, SEASONAL influenza, VIRUS diseases, LUNG infections, INFLUENZA vaccines
مستخلص: 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. [ABSTRACT FROM AUTHOR]
Copyright of Proceedings of the National Academy of Sciences of the United States of America is the property of National Academy of Sciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
قاعدة البيانات: Complementary Index
الوصف
تدمد:00278424
DOI:10.1073/pnas.1904022116