Health Science Reviews

by Chloe Ash

Cancer has long outsmarted our best treatments, developing resistance through rapid mutations and hijacking the body’s defenses. One of these treatments is immunotherapy, which can activate, recruit or inhibit suppression of important immune cells to target cancerous cells and enhance the anti-tumour response. 

Key players in this response include:

Cytotoxic T-cells (CD8+ T-cells) fight against foreign cells, such as cancerous cells. 

Dendritic cells present antigens to T-cells to activate them and induce an anti-tumour response. Regulatory B-cells and T-cells (Bregs and Tregs) bind to immune checkpoints, resulting in the suppression of immune cells to prevent unnecessary overactivation.  

Previous work by this group showed that an active lung infection in mice caused immune cells to move away from a tumour site and to the site of infection. This informed their current work, where they challenged mice with lung melanomas (lung Ca) and administered active influenza virus intranasally. Interestingly, mice withoutan active lung infection had both significantly higher lung cancer-specific and overall mortality when compared to those with both disease states. However, these results did not translate to skin melanomas when the virus was administered intratumorally, presumably because the virus could not infect skin cells and thus engage the necessary immune response as seen in the lung. 

Additional tests showed that an active infection was not necessary to achieve these results. Using the influenza vaccine containing the inactivated virus, they observed an increase in immune cells in the tumour microenvironment, where there was previously no infiltration, resulting in a decrease in tumour size. In short, they successfully converted a cold tumour to a hot one! Now, coupled with the use of immunotherapy, specifically a PD-L1 checkpoint inhibitor, the tumour size was significantly decreased and sustained. Not only is this groundbreaking in cancer therapy, but intratumoral administration of the vaccine maintains its protective effects against the influenza virus. 

These results offer a promising new avenue in overcoming immunologically cold tumours and sensitising them to immunotherapy through repurposing a commercially available vaccine that is safe, affordable and easily accessible. It seems that scientists may need to step out of the laboratories and search our pharmacies for innovative solutions with what we have! 

References:

J.H. Newman, C.B. Chesson, N.L. Herzog, P.K. Bommareddy, S.M. Aspromonte, R. Pepe, R. 

Estupinian, M.M. Aboelatta, S. Buddhadev, S. Tarabichi, M. Lee, S. Li, D.J. Medina, E.F. Giurini, 

K.H. Gupta, G. Guevara-Aleman, M. Rossi, C. Nowicki, A. Abed, J.W. Goldufsky, J.R. Broucek, R.E. Redondo, D. Rotter, S.R. Jhawar, S. Wang, F.J. Kohlhapp, H.L. Kaufman, P.G. Thomas, V. Gupta, T.M. Kuzel, J. Reiser, J. Paras, M.P. Kane, E.A. Singer, J. Malhotra, L.K. Denzin, D.B. 

Sant’Angelo, A.B. Rabson, L.Y. Lee, A. Lasfar, J. Langenfeld, J.M. Schenkel, M.J. Fidler, E.S. 

Ruiz, A.L. Marzo, J.S. Rudra, A.W. Silk, 

& A. Zloza, Intratumoral injection of the seasonal flu shot converts immunologically cold tumors to hot and serves as an immunotherapy for cancer, Proc. Natl. Acad. Sci. U.S.A. 117 (2) 1119-1128, https://doi.org/10.1073/pnas.1904022116 (2020).