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:PRAME Expression in Merkel Cell Carcinoma: Correlation With MCPyV Status, PD-L1, and Tumor-Infiltrating Lymphocytes in a Multicenter Cohort.
PRAME Expression in Merkel Cell Carcinoma: Correlation With MCPyV Status, PD-L1, and Tumor-Infiltrating Lymphocytes in a Multicenter Cohort.
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黑色素瘤优先表达抗原(PRAME)在 Merkel 细胞癌(MCC)中的表达已有描述,但其临床病理及生物学意义仍未完全明确。
我们研究了 PRAME 在 MCC 中的表达及其与 Merkel 细胞多瘤病毒(MCPyV)状态、PD-L1 表达、TIL(肿瘤浸润淋巴细胞)(TILs)、临床病理特征和临床结局的关系。回顾性分析了来自 3 个中心的 35 例 MCC 病例。重新评估了组织病理学特征以及 PRAME、PD-L1、MCPyV 和 p53 的免疫组化表达。PRAME 阳性定义为染色范围评分为 3+ 或 4+ 且至少为中等染色强度。TILs 在苏木精-伊红切片上进行评估。对临床病理相关性进行了统计学评估,并使用 Kaplan-Meier 和 Cox 回归方法分析总生存期和远处无转移生存期。
在 33 例可评估肿瘤中,10 例(30.3%)检出 PRAME 表达。大多数阳性病例显示弥漫性核染色,尽管有 1 例肿瘤表现出异质性 PRAME 表达。51.4% 的病例可见 MCPyV 阳性,PRAME 表达在 MCPyV 阳性肿瘤中更为常见(P=0.057)。PRAME/PD-L1 联合阳性与更高的 TIL 密度相关(P=0.018)。PRAME 表达与临床病理参数或生存无关。较低的 PD-L1 表达(CPS <1)与较短的总生存期独立相关。PRAME 在约三分之一的 MCC 中表达。PRAME 表达与生存结局无独立相关性。其在 MCPyV 阳性肿瘤中较高的表达率以及与部分免疫相关参数的关联值得进一步研究。
Preferentially expressed antigen in melanoma (PRAME) expression has been described in Merkel cell carcinoma (MCC), but its clinicopathologic and biological significance remains incompletely characterized.
We investigated PRAME expression in MCC and its relationship with Merkel cell polyomavirus (MCPyV) status, PD-L1 expression, tumor-infiltrating lymphocytes (TILs), clinicopathologic features, and clinical outcome. Thirty-five MCC cases from 3 centers were retrospectively reviewed. Histopathologic features and immunohistochemical expression of PRAME, PD-L1, MCPyV, and p53 were reassessed. PRAME positivity was defined as staining extent scores of 3+ or 4+ combined with at least moderate staining intensity. TILs were evaluated on hematoxylin and eosin sections. Clinicopathologic correlations were assessed statistically, and overall survival and distant metastasis-free survival were analyzed using Kaplan-Meier and Cox regression methods. PRAME expression was identified in 10 of 33 evaluable tumors (30.
3%). Most positive cases showed diffuse nuclear staining, although one tumor demonstrated heterogeneous PRAME expression. MCPyV positivity was seen in 51. 4% of cases, and PRAME expression was more frequent in MCPyV-positive tumors (P=0. 057). Combined PRAME/PD-L1 positivity was associated with higher TIL density (P=0. 018). PRAME expression was not associated with clinicopathologic parameters or survival.
Lower PD-L1 expression (CPS <1) was independently associated with shorter overall survival. PRAME was expressed in approximately one-third of MCCs. PRAME expression was not independently associated with survival outcomes. Higher expression rates in MCPyV-positive tumors and associations with selected immune-related parameters warrant further investigation.
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