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
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...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:785620b69a25494cb0d478afd06f6aae2021-11-11T08:18:25ZTopical 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 Microenvironment2234-943X10.3389/fonc.2021.754770https://doaj.org/article/785620b69a25494cb0d478afd06f6aae2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.754770/fullhttps://doaj.org/toc/2234-943XThe 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.Guoying NiGuoying NiGuoying NiGuoying NiXiaosong LiuXiaosong LiuHejie LiHejie LiConor E. FogartyConor E. FogartyShu ChenPingping ZhangYing LiuXiaolian WuMing Q. WeiGuoqiang ChenPing ZhangTianfang WangTianfang WangFrontiers Media S.A.articleTC-1 tumoursingle cell RNA sequencingcaerin peptidequantitative proteomicstumour microenvironmentNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
TC-1 tumour single cell RNA sequencing caerin peptide quantitative proteomics tumour microenvironment Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 |
| spellingShingle |
TC-1 tumour single cell RNA sequencing caerin peptide quantitative proteomics tumour microenvironment Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Guoying Ni Guoying Ni Guoying Ni Guoying Ni Xiaosong Liu Xiaosong Liu Hejie Li Hejie Li Conor E. Fogarty Conor E. Fogarty Shu Chen Pingping Zhang Ying Liu Xiaolian Wu Ming Q. Wei Guoqiang Chen Ping Zhang Tianfang Wang Tianfang Wang 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 |
| description |
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. |
| format |
article |
| author |
Guoying Ni Guoying Ni Guoying Ni Guoying Ni Xiaosong Liu Xiaosong Liu Hejie Li Hejie Li Conor E. Fogarty Conor E. Fogarty Shu Chen Pingping Zhang Ying Liu Xiaolian Wu Ming Q. Wei Guoqiang Chen Ping Zhang Tianfang Wang Tianfang Wang |
| author_facet |
Guoying Ni Guoying Ni Guoying Ni Guoying Ni Xiaosong Liu Xiaosong Liu Hejie Li Hejie Li Conor E. Fogarty Conor E. Fogarty Shu Chen Pingping Zhang Ying Liu Xiaolian Wu Ming Q. Wei Guoqiang Chen Ping Zhang Tianfang Wang Tianfang Wang |
| author_sort |
Guoying Ni |
| 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 |
| title_short |
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 |
| title_full |
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 |
| title_fullStr |
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 |
| title_full_unstemmed |
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 |
| title_sort |
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 |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/785620b69a25494cb0d478afd06f6aae |
| work_keys_str_mv |
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