CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：VISTA+/CD8+ status correlates with favorable prognosis in Epithelial ovarian cancer.
VISTA+/CD8+ status correlates with favorable prognosis in Epithelial ovarian cancer.
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通过阻断免疫检查点调节因子的免疫疗法已成为某些癌症的新型靶向治疗。其中，V域Ig抑制因子T细胞活化（VISTA）被鉴定为卵巢癌中的一种新型检查点调节因子。
本研究旨在探讨VISTA在上皮性卵巢癌（EOC）中的作用，及其与TIL（肿瘤浸润淋巴细胞）（TILs）标志物的关系和预后价值。通过免疫组织化学（IHC）评估了168例EOC组织微阵列（TMA）中VISTA、CD3、CD8、CD4、FOXP3和CD56的表达。
此外，分析了VISTA、TILs、临床病理变量和总生存期（OS）之间的关联。通过western blot评估了IGRov1细胞以及EOC患者PBMC中VISTA的表达。VISTA表达在64.28%的组织中检测到，其中42.3%为肿瘤细胞（TCs）阳性，47.9%为免疫细胞（ICs）阳性。在单变量分析中，VISTA表达与ICs中高密度的TILs：CD3+（p = 0.001）、CD4+（p = 0.002）和CD8+（p≤0.001）显著相关，但在TCs中不相关。在OS方面，多变量分析显示ICs中高密度CD8+ TILs与VISTA阳性染色之间存在显著关联（p = 0.044），但在TCs中不显著（p = 0.108）。
Kaplan-Meier曲线表明VISTA表达与ICs（p = 0.841）和TCs（p = 0.090）中延长的OS均无相关性。基于VISTA和CD8+TILs表达对EOC肿瘤微环境进行分类，显示出四种免疫亚型：VISTA+/CD8+、VISTA+/CD8-、VISTA-/CD8+和VISTA-/CD8-。双阳性 VISTA+/CD8+ 亚型在 TCs 和 ICs 中均与延长的 OS 显著相关（分别为 p = 0,012 和 p≤0,01），而 VISTA+/CD8- 患者的 OS 最差。
我们的结果显示，VISTA 在 IGRov1 细胞系和一名 EOC 患者的 LT-CD8 中高表达。我们的结果突出了 EOC 中 VISTA 表达与 CD8+ TILs 的关联，VISTA+/CD8+ 患者具有延长的 OS，并提出 VISTA 作为 EOC 潜在的免疫治疗靶点。
Immunotherapy by blocking immune checkpoint regulators has emerged as a new targeted therapy for some cancers. Among them V-domain Ig suppressor of Tcell activation (VISTA) which is identified as a novel checkpoint regulator in ovarian cancer.
This study aimed to investigate the VISTA role in Epithelial ovarian cancer (EOC), and its relationship with tumor-infiltrating lymphocytes (TILs) markers and its prognostic value. The expression of VISTA, CD3, CD8, CD4, FOXP3, and CD56 was assessed in 168 EOC tissue microarrays (TMA) by immunohistochemistry (IHC).
In addition, associations between VISTA, TILs, clinicopathological variables, and overall survival (OS) were analyzed. VISTA expression in IGRov1 cells, as well as in PBMC of EOC patient, was evaluated by western blot. VISTA expression was detected in 64,28% of tissues, among which 42. 3% were positive for tumor cells (TCs), and 47,9% were positive for immune cells (ICs). In univariate analysis, VISTA expression was significantly associated with a high density of TILs:CD3+ (p = 0,001), CD4+ (p = 0,002) and CD8+ (p≤0,001), in ICs but not in TCs.
In terms of OS, multivariate analysis showed a significant association between the high density of CD8+ TILs and VISTA positive staining in ICs (p = 0,044), but not in TCs (p = 0,108). Kaplan-Meier curves demonstrated no correlation between VISTA expression and prolonged OS in both ICs (p = 0,841) and TCs (p = 0,090).
Classification of EOC tumor microenvironment based on VISTA and CD8+TILs expression, demonstrated four immune subtypes: VISTA+/CD8+, VISTA+/CD8-, VISTA-/CD8+ and VISTA-/CD8-. The dual positive VISTA+/CD8+ subtype was significantly associated with prolonged OS in both TCs and ICs (p = 0,012 and p≤0,01, respectively), whereas patients with VISTA+/CD8- had the worst OS.
Our results showed that VISTA is highly expressed in the IGRov1 cell line and LT-CD8 from a patient with EOC.
Our results highlighted the association of VISTA expression and CD8+ TILs in EOC, with prolonged OS in patients with VISTA+/CD8+ and proposed VISTA as a potential immunotherapeutic target in EOC.
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