CD248基因在多種類型的間質細胞(mesenchymal cell)中表達，包括癌症相關的纖維母細胞（cancer-associated fibroblasts, CAFs），常與癌症的預後不佳有關，其中介導了發炎反應的發生或者細胞外間質的重塑。本篇研究透過觀察癌相關纖維母細胞在胰臟癌當中的組成比例及Cd248對癌細胞免疫抑制功能的影響。Cd248對促進癌症的轉移和遷移有重要影響，在過去是被認為與癌細胞的上皮-間質轉化（EMT）相關的特性，但近期的研究對逐漸重視藉由改變腫瘤微環境以抵抗宿主免疫系統攻擊的可能性。因此我們分析癌症基因組圖譜（TCGA）資料庫，針對胰臟癌的數據表示，CD248 基因高表達的患者總體存活率較低，以及免疫抑制標記的提高的情形。為了找出CD248對CAFs的占比及對癌細胞EMT狀態誘導的免疫抑制功能改變，我透過流式細胞技術（Flow cytometry, FCM）分析Cd248KO KPC胰臟癌小鼠模型的多種抗原的表達情形。在FCM數據中顯示，Cd248對於CAFs (CK19-; EpCAM-; PDGFR+)的組成無顯著影響。此外，Cd248WT KPC的平均腫瘤重量比Cd248KO KPC提高約1.40倍，並且癌細胞在腫瘤內所佔的比例更高。我的研究呈現Cd248+ CAFs對小鼠腫瘤內癌細胞增殖的作用。以Ki67 / PanCK對晚期PDAC切片進行的多重免疫螢光組織化學染色分析也證實Cd248+ CAFs對腫瘤增長的影響。因此，我未來將透過觀察癌細胞分泌的細胞激素是否對CAFs分化造成影響，並且了解Cd248是否干擾此過程的發生。

CD248 gene, expressed in several types of mesenchymal cells, including cancer-associated fibroblasts (CAFs), is related to a poor prognosis in cancer. CAFs mediate the occurrence of inflammation or the remodeling of extracellular matrix. Therefore, this study aims to observe the effects of Cd248 on the immunosuppressive function in cancer cells by observing the composition ratio of CAFs in mouse pancreatic tumors. Recent studies report that CD248 promotes cancer metastasis and migration in cancers. Tumoral epithelial–mesenchymal transition (EMT) in cancer cells may alter the tumor microenvironment against the host immune systems. Our database analysis of the The Cancer Genome Atlas (TCGA) pancreatic cancer cohort suggested that patients with high mRNA expression of CD248 associated with poor overall survival and increases of immunosuppressive markers. To identify potential effects of Cd248 on CAFs and immunosuppressive changes induced upon the cancer cells, I used the Cd248KO KPC mouse pancreatic cancer model and analyzed the cellular expression of multiple antigens by flow cytometry (FCM). Our FCM data showed that Cd248 had minor effects on the composition of CAFs (CK19-; EpCAM-; PDGFR+) in mouse tumors. Our data showed that the average tumor weight in Cd248WT KPC is about 1.40 folds heavier than in Cd248KO KPC; and the proportion of cancer cells in tumors is significantly higher. My results showed that Cd248 plays a role in the proliferation of cancer cells in the tumors. I also verify this finding by using Ki67/PanCK immunostains in multiple immunofluorescence histochemical staining of advanced PDAC sections. Therefore, I will observe whether cytokines secreted by cancer cells might affect the differentiation of CAFs to understand whether Cd248 interferes with this process.

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