Dataset Information

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): Q Exactive HF

ORGANISM(S): Mus Musculus (mouse)

SUBMITTER: Tianfang Wang

LAB HEAD: Tianfang Wang

PROVIDER: PXD025779 | Pride | 2022-02-17

REPOSITORIES: Pride

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Publications

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.

Ni Guoying G Liu Xiaosong X Li Hejie H Fogarty Conor E CE Chen Shu S Zhang Pingping P Liu Ying Y Wu Xiaolian X Wei Ming Q MQ Chen Guoqiang G Zhang Ping P Wang Tianfang T

Frontiers in oncology 20211111

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 <i>via</i> improving the tumour microenvironment. Confocal microscopy ...[more]

PMID: 34858827

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Project description:Cervical cancer (CC) is one of the most common malignancy in women worldwide. It is characterized by a natural continuous phenomenon, that is, it is in the initial stage of HPV infection, progresses to intraepithelial neoplasia, and then develops into invasion and metastasis. Determining the complexity of tumor microenvironment (TME) can deepen our understanding of lesion progression and provide novel therapeutic strategies for CC. We performed the single-cell RNA sequencing on the normal cervix, intraepithelial neoplasia, primary tumor and metastatic lymph node tissues to describe the composition, lineage, and functional status of immune cells and mesenchymal cells at different stages of CC progression. A total of 59913 single cells were obtained and divided into 9 cellular clusters, including immune cells (T/NK cells, macrophages, B cells, plasma cells, mast cells and neutrophils) and mesenchymal cells (endothelial cells, smooth muscle cells and fibroblasts). Our results showed that there were distinct cell subpopulations in different stages of CC. High-stage intraepithelial neoplasia (HSIL) tissue exhibited a low, recently activated TME, and it was characterized by high infiltration of tissue-resident CD8 T cell, effector NK cells, Treg, DC1, pDC, and M1-like macrophages. Tumor tissue displayed high enrichment of exhausted CD8 T cells, resident NK cells and M2-like macrophages, suggesting immunosuppressive TME. Metastatic lymph node consisted of naive T cell, central memory T cell, circling NK cells, cytotoxic CD8+ T cells and effector memory CD8 T cells, suggesting an early activated phase of immune response. This study is the first to delineate the transcriptome profile of immune cells during CC progression using single-cell RNA sequencing. Our results indicated that HSIL exhibited a low, recently activated TME, tumor displayed immunosuppressive statue, and metastatic lymph node showed early activated phase of immune response. Our study enhanced the understanding of dynamic change of TME during CC progression and has implications for the development of novel treatments to inhibit the initiation and progression of CC.

Dataset Information

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

Publications

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.

Similar Datasets

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