Topical Application of Temperature-Sensitive Gel Containing Caerin 1.1 and 1.9 Peptides on TC-1 Tumour-Bearing Mice Induced High-Level Immune Response in the Tumour Microenvironment

• Published in: Frontiers in oncology Vol. 11; p. 754770
• Main Authors: Ni, Guoying, Liu, Xiaosong, Li, Hejie, Fogarty, Conor E., Chen, Shu, Zhang, Pingping, Liu, Ying, Wu, Xiaolian, Wei, Ming Q., Chen, Guoqiang, Zhang, Ping, Wang, Tianfang
• Format: Journal Article
• Language: English
• Published: Frontiers Media S.A 11.11.2021
• Subjects: caerin peptide; Oncology; quantitative proteomics; single cell RNA sequencing; TC-1 tumour; tumour microenvironment
• ISSN: 2234-943X; 2234-943X
• DOI: 10.3389/fonc.2021.754770

The development of topical cream drugs that increase the immune activation of tumour-infiltrating lymphocytes against tumour and chronic viral infection-associated lesions is of great immunotherapeutic significance. This study demonstrates that the topical application of a temperature-sensitive gel containing caerin 1.1 and 1.9 peptides reduces nearly 50% of the tumour weight of HPV16 E6/E7-transformed TC-1 tumour-bearing mice via improving the tumour microenvironment. Confocal microscopy confirms the time-dependent penetration of caerin 1.9 through the epidermal layer of the ear skin structure of mice. Single-cell transcriptomic analysis shows that the caerin 1.1/1.9 gel expands the populations with high immune activation level and largely stimulates the pro-inflammatory activity of NK and dendritic cells. Closely associated with INFα response, Cebpb seems to play a key role in altering the function of all Arg1 hi macrophages in the caerin group. In addition, the caerin gel treatment recruits almost two-fold more activated CD8 + T cells to the TME, relative to the untreated tumour, which shows a synergistic effect derived from the regulation of S1pr1, Ccr7 , Ms4a4b and Gimap family expression. The TMT10plex-labelling proteomic quantification further demonstrates the activation of interferon-alpha/beta secretion and response to cytokine stimulus by the caerin gel, while the protein contents of several key regulators were elevated by more than 30%, such as Cd5l , Gzma , Ifit1 , Irf9 and Stat1 . Computational integration of the proteome with the single-cell transcriptome consistently suggested greater activation of NK and T cells with the topical application of caerin peptide gel.