Unknown

Dataset Information

0

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 | 2020-01-01

REPOSITORIES: biostudies

Similar Datasets

2016-01-01 | S-EPMC4930687 | BioStudies
2013-01-01 | S-EPMC3554683 | BioStudies
2016-01-01 | S-EPMC4951098 | BioStudies
2014-01-01 | S-EPMC4201984 | BioStudies
2011-01-01 | S-EPMC3197711 | BioStudies
2019-01-01 | S-EPMC6544376 | BioStudies
1000-01-01 | S-EPMC6149986 | BioStudies
2018-01-01 | S-EPMC6095604 | BioStudies
1000-01-01 | S-EPMC4514212 | BioStudies
1000-01-01 | S-EPMC4028866 | BioStudies