PNAs: intratumoral injection of influenza vaccine or enhancement of anti-cancer immunotherapy

PD-1 checkpoint inhibitors are more effective in immunoinfiltrating "hot" cancer than in immunomild "cold" cancer Therefore, it is an important direction of immunooncology to develop a method to transform cancer from cold to hot Antiviral response provides a possible way to "start" tumor immune infiltration Intratumoral injection of antiviral pattern recognition pathway agonists can promote acute inflammation These drugs are currently in clinical trials, with mixed success or failure Newman et al Now report a study that uses direct intratumoral influenza vaccine to promote the infiltration of immune cells into tumors They point out that cancer-specific mortality in lung cancer patients with influenza is low, and they also hypothesize that exposure to influenza viruses may increase the immune infiltration of patients' tumors In a mouse model of melanoma with lung metastasis, they observed that nasal administration of an active influenza virus reduced the formation of lung metastases Injection of influenza virus into the tumor reduced the size of the tumor and increased the immune infiltration of dendritic cells (DC) and T cells These experiments were carried out with commercial inactivated vaccine, which has synergistic effect with PD-1 inhibition Interestingly, in their mouse models, tumor immunosuppression regulates the depletion of B cells, which is crucial for their antitumor effect When vaccinated in the tumor, the mice also retained the ability to provide anti influenza protection Based on these findings, the authors suggest that injecting a clinically approved influenza vaccine into a tumor to an accessible metastatic tumor will have dual benefits, providing anti influenza protection and anti-cancer immune infiltration This is a thought-provoking idea that can be easily translated into clinical trials However, to choose the right clinical environment to test the influenza injection, we need to answer some key questions first Given that the "cold" state of the immune system is caused by a variety of different immunosuppressive pathways, is the "cancer flu vaccine" effective only for those cold tumors that play a leading role in regulatory B cells? Is there genetic variation in cancer that promotes or suppresses response to influenza virus components? If they exist, can they be used as biomarkers of therapeutic sensitivity? Does simultaneous injection of virus components and PD-1 inhibitors aggravate immunotoxicity? Further validation in a carefully selected immune robust cancer model will help answer these questions Nevertheless, the safety of existing influenza vaccines provides an attractive choice for the simple transformation of cancer from "cold" to "hot" reference material: