免疫检查点阻断通过扩增效应 CD8⁺ T 细胞克隆增强淋巴细胞清除性化疗诱导的抗肿瘤免疫
Immune Checkpoint Blockade Augments Lymphodepleting Chemotherapy-Induced Antitumor Immunity by Expanding Effector CD8+ T-cell Clones.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Prognostic value of PD-L1, tumor-infiltrating lymphocytes, and CD117 in vulvovaginal melanoma.
Prognostic value of PD-L1, tumor-infiltrating lymphocytes, and CD117 in vulvovaginal melanoma.
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该研究确立 PD-L1 表达与 TIL 密度为外阴阴道黑色素瘤的独立预后因素,提示其可用于风险分层和治疗决策。
外阴阴道黑色素瘤是一种罕见且侵袭性强的黑色素瘤亚型,具有独特的突变模式(例如 KIT[CD117]突变频率较高),临床结局较差。本研究考察 PD-L1、TIL(肿瘤浸润淋巴细胞)及 CD117 表达对外阴阴道黑色素瘤患者预后的影响。
回顾性分析 2010 年 1 月至 2020 年 12 月经组织学确诊的外阴阴道黑色素瘤病例。采用免疫组织化学评估 PD-L1 和 CD117 表达,并依据已发表指南对 TIL 密度分级,同时评估 PD-L1 表达与主要临床病理特征的关联。主要结局为疾病特异性生存期,即从确诊至死于外阴阴道黑色素瘤的时间,采用 Kaplan-Meier 估计和 Cox 回归模型分析。
47 例患者中,70% 确诊时已为晚期(III–IV 期)。22 例(47%)检测到 PD-L1 表达,12 例(26%)存在旺盛的 TIL 浸润。PD-L1 阳性与晚期(p = .002)、TIL 浸润不旺盛或缺失(p = .003)以及淋巴血管侵犯(p = .047)相关。Kaplan-Meier 分析显示,PD-L1 阴性肿瘤患者的疾病特异性生存显著较好(3 年疾病特异性生存率:48% 对 18%,p = .008);TIL 浸润旺盛者亦显著较好(67% 对 21%,p = .003)。联合分层中,PD-L1 阴性且 TIL 浸润旺盛者预后最佳,PD-L1 阳性且 TIL 浸润不旺盛或缺失者预后最差(p < .001)。多变量分析中,PD-L1 表达(HR 1.68,95% CI 1.10–2.55,p = .015)、TIL 状态(HR 0.62,95% CI 0.43–0.89,p = .012)和疾病分期(HR 1.85,95% CI 1.22–2.81,p = .004)仍为独立预后因素。此外,30% 肿瘤(n = 14)呈 CD117 阳性,但其预后意义未能在多变量分析中保留。
研究确认 PD-L1 表达和 TIL 密度是独立预后因素,提示二者可能有助于风险分层和治疗决策。
Vulvovaginal melanoma represents a rare and aggressive melanoma subtype with distinct mutation patterns, such as a higher frequency of KIT (CD117) mutations, and is associated with poor clinical outcomes. This study investigated the prognostic implications of PD-L1 expression, tumor-infiltrating lymphocytes (TILs), and CD117 expression in patients with vulvovaginal melanoma.
A retrospective analysis was conducted on histologically confirmed vulvovaginal melanoma cases diagnosed between January 2010 and December 2020. Immunohistochemical evaluation was performed to assess PD-L1 and CD117 expression, while TIL density was graded using published guidelines. Associations between PD-L1 expression and key clinicopathological features were also evaluated. The primary outcome was disease-specific survival, defined as the interval from diagnosis to death specifically attributable to vulvovaginal melanoma, analyzed using Kaplan-Meier estimates and Cox regression models.
Among 47 patients, 70% presented with advanced-stage disease (stage III-IV). PD-L1 expression was detected in 22 patients (47%), and brisk TIL infiltration was observed in 12 patients (26%). PD-L1 positivity correlated with advanced disease stage (p = .002), non-brisk/absent TILs (p = .003), and lymphovascular invasion (p = .047). Kaplan-Meier analysis demonstrated significantly better disease-specific survival in PD-L1-negative tumors (3-year disease-specific survival: 48% vs 18%, p = .008) and in tumors with brisk TIL infiltration (3-year disease-specific survival: 67% vs 21%, p = .003). Combined stratification identified PD-L1-negative/brisk TIL tumors as the most favorable subgroup, while PD-L1-positive/non-brisk/absent TIL tumors exhibited the poorest prognosis (p < .001). In multivariate analysis, PD-L1 expression (HR 1.68, 95% CI 1.10 to 2.55, p = .015), TIL status (HR 0.62, 95% CI 0.43 to 0.89, p = .012), and disease stage (HR 1.85, 95% CI 1.22 to 2.81, p = .004) remained independent prognostic factors. Additionally, CD117 positivity was observed in 30% of tumors (n = 14), although its prognostic significance was not retained in multivariate analysis.
The study establishes PD-L1 expression and TIL density as independent prognostic factors in vulvovaginal melanoma, suggesting their potential utility for risk stratification and therapeutic decision-making.
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