Maximizing Efficacy of Cancer Nanovaccines and Immune Cells Landscape in Responders and Non-Responders to Immunotherapy.

Adjuvants, formulations, and processing of tumor antigens (collection, lysis, purification, and oxidation) can affect the therapeutic efficacy of cancer vaccines. To maximize their efficacy, adjuvants and their combinations are investigated to prepare vaccines with whole tumor antigens. By comparing different nano/micro-vaccines, ≤ 400 nm and 2.5 µm, respectively, are identified as their optimal sizes. When used alone, the optimal cancer vaccine cures all or most tumor-bearing mice with melanoma, lung cancer, pancreatic cancer, and melanoma lung metastasis. The landscape of immune cells in the blood, splenocytes, and draining lymph nodes of vaccine-treated mice is systematically investigated using single-cell sequencing. The diversity of CD8⁺ T cell receptors (TCR), CD4⁺ TCR, and B cell receptors (BCR) in cured mice is higher than that in uncured mice. By comparing 21 samples, several biomarkers, including KLRG1, S100A4, S1PR5, IL2Ra, and IKZF2, were identified to distinguish responders and non-responders to immunotherapy. Moreover, S100A4, S1PR5 and KLRG1, are biomarkers of therapeutic efficacy in mouse cancer models and patients with cancer. Hence, this study presents an optimized cancer vaccine that cures most tumor-bearing mouse models and the landscape of immune cells in non-responders and responders to immunotherapy. The results of this study will help to develop better cancer vaccines.