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By comparing different nano\/micro\u2010vaccines, \u2264 400 nm and 2.5 \u00b5m, respectively, are identified as their optimal sizes. When used alone, the optimal cancer vaccine cures all or most tumor\u2010bearing 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\u2010treated mice is systematically investigated using single\u2010cell sequencing. The diversity of CD8<jats:sup>+<\/jats:sup> T cell receptors (TCR), CD4<jats:sup>+<\/jats:sup> 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\u2010responders to immunotherapy. Moreover, S100A4, S1PR5 and KLRG1, are biomarkers of therapeutic efficacy in mouse cancer models and patients with cancer. 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