Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China.
Department of Biochemistry and Molecular Biology, NHC Key Laboratory of Glycoconjugate Research, School of Basic Medical Sciences, Fudan University, Shanghai, China.
BMC Cancer. 2023 Jul 14;23(1):661. doi: 10.1186/s12885-023-11157-x.
V domain Immunoglobulin suppressor of T cell activation (VISTA) has been proved to be a novel immune checkpoint molecule that positively regulates T cell infiltration in several malignancies. However, the clinical impact of VISTA on muscle-invasive bladder cancer (MIBC) patients remains relatively obscure.
This study enrolled 135 MIBC patients from Zhongshan Hospital (ZSHS) and 391 patients from The Cancer Genome Atlas (TCGA) to examine the VISTA expression and immune contexture based on immunohistochemistry (IHC) staining and CIBERSORT algorithm. Additionally, IMvigor210 Cohort included 195 bladder-derived urothelial carcinoma patients to evaluate the efficacy of immunotherapy. Kaplan-Meier curve and Cox regression analyses were conducted to assess clinical outcomes.
MIBC patients with high VISTA immune cells (ICs) possessed poor overall survival and inferior therapeutic responsiveness to adjuvant chemotherapy (ACT), but superior responsiveness to PD-L1 inhibitor. VISTA ICs infiltration shaped an immunoevasive context featured by regulatory T cells (Tregs), M2 macrophages, mast cells and exhausted CD8 T cells infiltration, with increased interleukin 10 (IL-10), transforming growth factor-β (TGF-β) and interferon-γ (IFN-γ), but also elevated T-cell immunoglobulin mucin-3 (TIM-3), lymphocyte activation gene 3 (LAG-3) and T-cell immunoglobulin and ITIM domain (TIGIT), which was also mainly presented in basal-squamous and luminal-infiltrated subtypes of MIBC.
VISTA ICs infiltration could be an independent predictor to identify poor prognosis and therapeutic responses (PD-L1 blockade and ACT) in MIBC patients, which was associated with immunoevasive contexture. The novel immune checkpoint VISTA might be utilized as a candidate treatment biomarker in MIBC patients.
V 结构域免疫球蛋白 T 细胞活化抑制因子（VISTA）已被证明是一种新型免疫检查点分子，可正向调节几种恶性肿瘤中的 T 细胞浸润。然而，VISTA 对肌层浸润性膀胱癌（MIBC）患者的临床影响仍相对不清楚。
本研究纳入了来自中山医院（ZSHS）的 135 例 MIBC 患者和来自癌症基因组图谱（TCGA）的 391 例患者，基于免疫组织化学（IHC）染色和 CIBERSORT 算法检测 VISTA 的表达和免疫微环境。此外，IMvigor210 队列纳入了 195 例膀胱尿路上皮癌患者，以评估免疫治疗的疗效。采用 Kaplan-Meier 曲线和 Cox 回归分析评估临床结局。
高 VISTA 免疫细胞（IC）浸润的 MIBC 患者总生存较差，对辅助化疗（ACT）的治疗反应较差，但对 PD-L1 抑制剂的反应较好。VISTA ICs 浸润形成了一种免疫逃避的微环境，其特征是调节性 T 细胞（Tregs）、M2 巨噬细胞、肥大细胞和耗竭的 CD8 T 细胞浸润，同时伴有白细胞介素 10（IL-10）、转化生长因子-β（TGF-β）和干扰素-γ（IFN-γ）的增加，也伴随着 T 细胞免疫球蛋白粘蛋白-3（TIM-3）、淋巴细胞激活基因 3（LAG-3）和 T 细胞免疫球蛋白和 ITIM 结构域（TIGIT）的增加，这些主要存在于 MIBC 的基底鳞状和腔浸润亚型中。
VISTA ICs 浸润可作为识别 MIBC 患者不良预后和治疗反应（PD-L1 阻断和 ACT）的独立预测因子，与免疫逃避微环境有关。新型免疫检查点 VISTA 可作为 MIBC 患者的候选治疗生物标志物。
