Topical application of temperature sensitive gel containing caerin 1.1 and 1.9 peptides on TC-1 tumour bearing mice modulates heterogeneity of macrophage and dendritic cell in the tumour microenvironment

ABSTRACT: In this study, we demonstrate that, the topical application of a temperature-sensitive gel containing caerin 1.1 and 1.9 peptides significantly reduces the tumour weight of HPV 16 E6/E7 transformed TC-1 tumour bearing mice via improving the tumour microenvironment (TME) when compared with untreated tumour or a control peptide-containing gel. We use single cell transcriptomics and TMT10 plex-labelling proteomics to quantify changes in cellular activity across different cell types within the TME. We show that caerin 1.1/1.9 gel increased immune activating macrophages, modulated the heterogeneity of NK and dendritic cells to be more pro-inflammatory, and increased numbers of activated CD8+ T cells. Proteomic profiling demonstrated higher innate immune responses, especially the positive regulations of interferon-alpha/beta secretion and response to cytokine stimulus in the caerin gel groups. Further, computational integration of the proteome with the single cell transcriptome consistently suggested more activated T cells and NK cells with the treatment of caerin peptide gel.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

SUBMITTER: Tianfang Wang  

LAB HEAD: Tianfang Wang

PROVIDER: PXD025779 | Pride | 2022-02-17

REPOSITORIES: Pride