Cancer vaccines promise a broad and affordable alternative to protein and cell-based cancer immunotherapies. Utilizing SNP-7/8a, a self-assembling nanoparticle vaccine that combined expression of an engineered cancer neoantigen with a Toll-like receptor 7/8 agonist, Baharom and colleagues revealed separable importance for both CD8+ T cells and innate signaling in mediating therapeutic efficacy. Subcutaneous delivery of SNP-7/8a was sufficient to elicit a CD8+ T-cell response equivalent to intravenous SNP-7/8a. However, only intravenous delivery led to accumulation of SNP in tumors, leading to a systemic increase in inflammatory cytokines, most importantly, IFNα. Antibody blockade of IFNα signaling reversed the efficacy of intravenous SNP, as IFNα was necessary for the reduction of a subset of immunosuppressive (Chil3+) monocytes within tumors. Patients with renal cell or glial tumors expressing high levels of Chil3 exhibited worse prognoses.
Expert Commentary: Effective cancer vaccines require generating antitumor CD8+ T cells and...