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標題: | 探查PD-L1表現量對與EB病毒相關的多種癌症的影響 To investigate the influence of PD-L1 expression in several cancers associated with Epstein-Barr virus |
作者: | 林子強 Zi-Qiang Lin |
指導教授: | 蔡錦華 Ching-Hwa Tsai |
關鍵字: | EB病毒,PD-L1,腫瘤浸潤免疫細胞,M1型巨噬細胞, Epstein-Barr virus (EBV),Programmed death-ligand 1 (PD-L1),Tumor-infiltrating immune cells,Macrophages M1, |
出版年 : | 2023 |
學位: | 碩士 |
摘要: | EB病毒(Epstein-Barr virus)是一種廣泛感染人群並可能有致癌能力的人類皰疹病毒,因其主要感染人類之B細胞以及上皮細胞,所以與多種B淋巴細胞癌以及上皮細胞癌具有顯著的相關性。本實驗室先前研究顯示,B細胞之免疫抑制分子,細胞程式死亡-配體1(PD-L1)的表現量會受到EB病毒感染而顯著提升。因此,本研究蒐集與EB病毒相關的多種癌症,包括瀰漫性大B細胞淋巴瘤、經典霍奇金氏淋巴瘤、鼻咽癌以及胃癌之cDNA微陣列以及生存資訊資料集,旨在探查PD-L1表現量對這些癌症患者生存率是否具有影響。首先,本研究確認,EB病毒與胃癌之PD-L1的高表現量相關。本研究進而通過生存分析發現,PD-L1在多種可能與EB病毒相關的癌症之資料集中,均不會影響患者的總生存期。並且在部分胃癌資料集GSE84437中,PD-L1的較高表現量與患者較長的總生存期呈正相關。由於PD-L1在腫瘤免疫微環境中,不僅表現於腫瘤細胞上,還表現在以免疫細胞為主的腫瘤浸潤細胞中,因此本研究所探討的腫瘤免疫微環境總PD-L1表現量包括腫瘤細胞及腫瘤浸潤細胞的表現。在本研究使用的所有可能與EB病毒相關的癌症之資料集中,腫瘤免疫微環境的總PD-L1表現量,均與具有可能腫瘤抑制作用的M1型巨噬細胞之浸潤量呈正相關,表示可能為患者較好的預後因子。此外,本研究也發現,總PD-L1的表現量,也與腫瘤浸潤CD8+ T細胞之PD-L1配體PD-1(細胞程式死亡-1)的表現量呈正相關,表示可能為患者較差的預後因子。以上結果表明,總PD-L1在多種與EB病毒相關之癌症中,總PD-L1同時與較好和較差的預後因子顯著相關。同時本研究也發現,EB病毒影響並降低了總PD-L1表現量與M1型巨噬細胞浸潤量之相關性,證實EB病毒可能上調腫瘤細胞之PD-L1表現量。綜合以上研究結果,本研究發現,腫瘤免疫微環境之總PD-L1表現量在多種與EB病毒相關之癌症中,可能同時與較好和較差的預後因素有關。亦即,總PD-L1表現量可作為一把雙刃劍,其表現量對與EB病毒相關的多種癌症可能同時具有兩種看似相反的影響。 Epstein-Barr virus (EBV) is a widely infective human herpesvirus with oncogenic potential. The virus primarily infects human B cells and epithelial cells, and its infection is significantly associated with various B-cell lymphomas and carcinomas. Previous cDNA microarray data performed in our laboratory have shown that the expression of programmed death-ligand 1 (PD-L1), an immune checkpoint molecule in B cells, is significantly upregulated upon EBV infection. Therefore, this study collected cDNA microarray and survival information datasets related to various EBV-associated cancers, including diffuse large B-cell lymphoma, classical Hodgkin lymphoma, nasopharyngeal carcinoma, and gastric carcinoma, with the aim of investigating the influence of PD-L1 expression. Firstly, this study confirmed the association between EBV and high PD-L1 expression in gastric carcinoma, a clinical report. Furthermore, survival analysis revealed that PD-L1 did not shorten the overall survival rate of patients in the datasets of several cancers possibly related to EBV. In a subset of gastric carcinoma datasets GSE84437, higher PD-L1 expression was associated with longer overall survival. The PD-L1 expression investigated in this study refers to the total PD-L1 expression in the tumor immune microenvironment since PD-L1 is expressed not only on tumor cells but also on tumor-infiltrating immune cells in the tumor immune microenvironment. Analysis of tumor-infiltrating immune cells showed that in all the datasets of possible EBV-associated cancers used in this study, the total PD-L1 expression in the tumor immune microenvironment was positively correlated with the infiltration of M1 macrophages, which have tumor-suppressive effects, possibly as a good prognostic factor. The total PD-L1 expression was also positively correlated with the expression of PD-1 (programmed death-1), the ligand of PD-L1, on tumor-infiltrating CD8+ T cells, possibly as a poor prognostic factor. These results indicated that the total PD-L1 expression is significantly associated with both better and worse prognostic factors in various EBV-associated cancers. Furthermore, this study hinted that EBV may influence the correlation between total PD-L1 expression and the amounts of infiltrated M1 macrophages, suggesting that EBV upregulates PD-L1 expression on tumor cells. In conclusion, this study discovered that the total PD-L1 expression in the tumor immune microenvironment may be simultaneously associated with both better and worse prognostic factors in various EBV-related cancers. In other words, the expression of total PD-L1 may have dual effects, exerting opposite influences on multiple EBV-associated cancers. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/89208 |
DOI: | 10.6342/NTU202302598 |
全文授權: | 未授權 |
顯示於系所單位: | 微生物學科所 |
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