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Kill shot: Flu vaccine is a stone cold cancer killer

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Science Immunology  07 Feb 2020:
Vol. 5, Issue 44, eabb0239
DOI: 10.1126/sciimmunol.abb0239

Abstract

Injection of seasonal influenza vaccine into tumors enhances local and systemic anti-cancer immunity and sensitizes previously resistant tumors to immune checkpoint therapy.

Immune checkpoint cancer therapies work well in patients with “hot” tumors, those infiltrated by pro-inflammatory immune cells, but do not work well in patients with “cold” tumors, those that lack immune cells or are heavily infiltrated by immunosuppressive cells. Therapies that convert cold tumors to hot ones are needed to save cancer patients who are not helped by current approaches. Building on laboratory studies and clinical observations that lung cancer patients who developed influenza lived longer, the authors injected tumors with influenza and studied the effects on anticancer immunity. In mouse models of melanoma and breast cancer, injection of heat-inactivated influenza into tumors inhibited tumor growth, reduced metastases, and enhanced responses to immune checkpoint blockade therapy by increasing antigen presentation, CD8+ T cells, and cross-presenting DC. Live influenza induced less TLR7 signaling and did not enhance antitumor responses. Intratumoral injection of the FDA-approved seasonal flu vaccine had similar effects, converted cold tumors to hot, and as a bonus, protected against influenza. Surprisingly, a squalene-adjuvanted influenza vaccine did not enhance anticancer responses; regulatory B cells in the tumor skewed responses toward antibody production instead of enhancing T cell responses. These studies demonstrate the promise of using “bugs as drugs,” an approach that leverages antipathogen responses to boost flagging tumor immunity.

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