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

Guoying Ni; Xiaosong Liu; Hejie Li; Conor E Fogarty; Shu Chen; Pingping Zhang; Ying Liu; Xiaolian Wu; Ming Q Wei; Guoqiang Chen; Ping Zhang; Tianfang Wang

doi:10.3389/fonc.2021.754770

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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

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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

Guoying Ni, Xiaosong Liu, Hejie Li, Conor E Fogarty, Shu Chen, Pingping Zhang, Ying Liu, Xiaolian Wu, Ming Q Wei, Guoqiang Chen, …

Frontiers in Oncology, Vol.11, pp.1-19

2021

DOI: https://doi.org/10.3389/fonc.2021.754770

PMCID: PMC8632150

PMID: 34858827

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Abstract

TC-1 tumour

single cell RNA sequencing

caerin peptide

quantitative proteomics

tumour microenvironment

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 Arg1hi 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.

Details

Title: 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
Authors: Guoying Ni (Author) - University of the Sunshine Coast, Queensland, GeneCology Research Centre - Legacy
Xiaosong Liu (Author) - University of the Sunshine Coast, Queensland, GeneCology Research Centre - Legacy
Hejie Li (Author) - University of the Sunshine Coast, Queensland, GeneCology Research Centre - Legacy
Conor E Fogarty (Author) - University of the Sunshine Coast, Queensland, GeneCology Research Centre - Legacy
Shu Chen (Author) - First People's Hospital of Foshan
Pingping Zhang (Author) - First People's Hospital of Foshan
Ying Liu (Author) - First People's Hospital of Foshan
Xiaolian Wu (Author) - First People's Hospital of Foshan
Ming Q Wei (Author) - Griffith University
Guoqiang Chen (Author) - First People's Hospital of Foshan
Ping Zhang (Author) - First People's Hospital of Foshan
Tianfang Wang (Author) - University of the Sunshine Coast, Queensland, GeneCology Research Centre - Legacy
Publication details: Frontiers in Oncology, Vol.11, pp.1-19
Publisher: Frontiers Research Foundation
Date published: 2021
DOI: 10.3389/fonc.2021.754770
ISSN: 2234-943X
PMID: 34858827; PMC8632150
Copyright note: Copyright © 2021 Ni, Liu, Li, Fogarty, Chen, Zhang, Liu, Wu, Wei, Chen, Zhang and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Organisation Unit: School of Science and Engineering - Legacy; University of the Sunshine Coast, Queensland; GeneCology Research Centre - Legacy; School of Science, Technology and Engineering; Centre for Bioinnovation
Language: English
Record Identifier: 99598307402621
Output Type: Journal article

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