1. The immunomodulatory role of paracrine signalling factor VSIG4 in peritoneal metastases
- Author
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Yik Yan Chong, Sasinthiran Thiagarajan, Qiu Xuan Tan, Hui Jun Lim, Joey Wee-Shan Tan, Josephine Hendrikson, Gillian Ng, Ying Liu, Clara Yieh Lin Chong, Wanyu Guo, Nye Thane Ngo, Wei-Qiang Leow, Tracy Loh, Xin Xiu Sam, Tony Kiat Hon Lim, Mingzhe Cai, Chin Jin Seo, Jolene Si Min Wong, Khee Chee Soo, Claramae Shulyn Chia, Nicholas Brian Shannon, and Chin-Ann Johnny Ong
- Subjects
Medicine ,Science - Abstract
Abstract Peritoneal metastasis (PM), the regional progression of intra-abdominal malignancies, is a common sequelae of colorectal cancer (CRC). Immunotherapy is slated to be effective in generating long-lasting anti-tumour response as it utilizes the specificity and memory of the immune system. In the tumour microenvironment, tumour associated macrophages (TAMs) are posited to create an anti-inflammatory pro-tumorigenic environment. In this paper, we aimed to identify immunomodulatory factors associated with colorectal PM (CPM). A publicly available colorectal single cell database (GSE183916) was analysed to identify possible immunological markers that are associated with the activation of macrophages in cancers. Immunohistochemical analysis for V-set and immunoglobin containing domain 4 (VSIG4) expression was performed on tumour microarrays (TMAs) of tumours of colorectal origin (n = 211). Expression of VSIG4 in cell-free ascites obtained from CPM patients (n = 39) was determined using enzyme-linked immunosorbent assay (ELISA). CD163-positive TAMs cluster expression was extracted from a publicly available single cell database and evaluated for the top 100 genes. From these macrophage-expressed genes, VSIG4, a membrane protein produced by the M2 macrophages, mediates the up-regulation of anti-inflammatory and down-regulation of pro-inflammatory macrophages, contributing to an overall anti-inflammatory state. CRC TMA IHC staining showed that low expression of VSIG4 in stromal tissues of primary CRC are associated with poor prognosis (p = 0.0226). CPM ascites also contained varying concentrations of VSIG4, which points to a possible role of VSIG4 in the ascites. The contribution of VSIG4 to CPM development can be further evaluated for its potential as an immunotherapeutic agent.
- Published
- 2024
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