%0 Journal Article %1 Newman:2019:Proc-Natl-Acad-Sci-U-S-A:31888983 %A Newman, J H %A Chesson, C B %A Herzog, N L %A Bommareddy, P K %A Aspromonte, S M %A Pepe, R %A Estupinian, R %A Aboelatta, M M %A Buddhadev, S %A Tarabichi, S %A Lee, M %A Li, S %A Medina, D J %A Giurini, E F %A Gupta, K H %A Guevara-Aleman, G %A Rossi, M %A Nowicki, C %A Abed, A %A Goldufsky, J W %A Broucek, J R %A Redondo, R E %A Rotter, D %A Jhawar, S R %A Wang, S J %A Kohlhapp, F J %A Kaufman, H L %A Thomas, P G %A Gupta, V %A Kuzel, T M %A Reiser, J %A Paras, J %A Kane, M P %A Singer, E A %A Malhotra, J %A Denzin, L K %A Sant'Angelo, D B %A Rabson, A B %A Lee, L Y %A Lasfar, A %A Langenfeld, J %A Schenkel, J M %A Fidler, M J %A Ruiz, E S %A Marzo, A L %A Rudra, J S %A Silk, A W %A Zloza, A %D 2019 %J Proc Natl Acad Sci U S A %K cancer-research fulltext immunology immunotherapy shouldread vaccination %R 10.1073/pnas.1904022116 %T Intratumoral injection of the seasonal flu shot converts immunologically cold tumors to hot and serves as an immunotherapy for cancer %U https://www.ncbi.nlm.nih.gov/pubmed/31888983 %X 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.

@article{Newman:2019:Proc-Natl-Acad-Sci-U-S-A:31888983, 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.}, added-at = {2020-01-01T21:59:03.000+0100}, author = {Newman, J H and Chesson, C B and Herzog, N L and Bommareddy, P K and Aspromonte, S M and Pepe, R and Estupinian, R and Aboelatta, M M and Buddhadev, S and Tarabichi, S and Lee, M and Li, S and Medina, D J and Giurini, E F and Gupta, K H and Guevara-Aleman, G and Rossi, M and Nowicki, C and Abed, A and Goldufsky, J W and Broucek, J R and Redondo, R E and Rotter, D and Jhawar, S R and Wang, S J and Kohlhapp, F J and Kaufman, H L and Thomas, P G and Gupta, V and Kuzel, T M and Reiser, J and Paras, J and Kane, M P and Singer, E A and Malhotra, J and Denzin, L K and Sant'Angelo, D B and Rabson, A B and Lee, L Y and Lasfar, A and Langenfeld, J and Schenkel, J M and Fidler, M J and Ruiz, E S and Marzo, A L and Rudra, J S and Silk, A W and Zloza, A}, biburl = {https://www.bibsonomy.org/bibtex/2b077b9d71122d80f5457986af06086b3/marcsaric}, description = {Intratumoral injection of the seasonal flu shot converts immunologically cold tumors to hot and serves as an immunotherapy for cancer. - PubMed - NCBI}, doi = {10.1073/pnas.1904022116}, interhash = {abdec921da44276292e2e53e92f32ee9}, intrahash = {b077b9d71122d80f5457986af06086b3}, journal = {Proc Natl Acad Sci U S A}, keywords = {cancer-research fulltext immunology immunotherapy shouldread vaccination}, month = dec, pmid = {31888983}, timestamp = {2020-01-01T21:59:03.000+0100}, title = {Intratumoral injection of the seasonal flu shot converts immunologically cold tumors to hot and serves as an immunotherapy for cancer}, url = {https://www.ncbi.nlm.nih.gov/pubmed/31888983}, year = 2019 }