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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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    Author(s)
    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
    Griffith University Author(s)
    Wei, Ming Q.
    Ni, Guoying
    Zhang, Ping
    Year published
    2021
    Metadata
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    Abstract
    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 ...
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    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.
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    Journal Title
    Frontiers in Oncology
    Volume
    11
    DOI
    https://doi.org/10.3389/fonc.2021.754770
    Copyright Statement
    © 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.
    Subject
    Oncology and carcinogenesis
    TC-1 tumour
    caerin peptide
    quantitative proteomics
    single cell RNA sequencing
    tumour microenvironment
    Publication URI
    http://hdl.handle.net/10072/410722
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    • Journal articles

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