The development of vaccine formula that alter the tumour-infiltrating lymphocytes to be more immune active against the tumour is key to the improvement of immunotherapies and the prediction of clinical responses. Here, we demonstrate that in conjunction with PD-1 blockade, caerin 1.1 and 1.9 peptides increases the efficacy of a HPV16 E7 peptide based therapeutic vaccine containing interleukin-10 signalling blocker, via improving the TC-1 tumour microenvironment. We use single cell transcriptomics and mass spectrometry-based proteomics to quantify changes in cellular activity across 19 cell types. We show that the injection of caerin 1.1/1.9 leads to elevated immune activating macrophages and NK cells, while largely reducing immunosuppressive macrophage with M2 phenotype. We observe CD8+ T cells were more activated with higher populations of memory and effector-memory CD8+ T subsets. Proteomic profiling reveals the activation of Stat1 modulated apoptosis and implies the production of nitric oxide in tumour. Computational integration of the proteome with the single cell transcriptome predicts deactivation of immune suppressive B cell function by caerin 1.1 and 1.9.