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原发部位 CD8⁺ 肿瘤浸润淋巴细胞或可作为皮肤血管肉瘤的预后因素。

CD8⁺ tumor-infiltrating lymphocytes at primary sites as a possible prognostic factor of cutaneous angiosarcoma.

机构信息

Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.

出版信息

Int J Cancer. 2014 May 15;134(10):2393-402. doi: 10.1002/ijc.28581. Epub 2013 Nov 18.

Abstract

Tumor-infiltrating lymphocytes (TILs) have been reported as a prognostic factor in various cancers and are a promising target for immunotherapy. To investigate whether TILs have any impact on the prognosis of angiosarcoma patients, 55 non-treated patients (40 patients at stage 1 with cutaneous localized tumors, 4 patients at stage 2 with lymph node metastases and 11 patients at stage 3 with distant metastases) with angiosarcoma were evaluated retrospectively by immunohistochemistry stained CD4, CD8, FOXP3 and Ki67. The Kaplan-Meier method was used to estimate overall survival with patients at stage 1. Survival differences were analyzed by the log-rank test. Patients with higher numbers of CD8(+) TILs in their primary tumors survived significantly longer compared with patients with lower values. Moreover, the number of CD8 in TILs was positively correlated with a distant metastasis-free period. The total number of primary TILs (CD4 plus CD8) and CD8(+) primary TILs of stage 3 patients with distant metastases was positively correlated with their overall survival. To evaluate whether CD8(+) effector T cells are activated or differentiated, flow cytometric analysis of peripheral blood mononuclear cells (PBMC) was performed. The percentages of CD8(+) T cells producing IFN-γ in PBMC were significantly higher in patients with angiosarcoma (n = 10) compared not only with that of healthy controls (n = 20) but also patients with advanced melanoma (n = 11). These results suggest that anti-tumor immunity is clinically relevant in angiosarcoma.

摘要

肿瘤浸润淋巴细胞(TILs)已被报道为多种癌症的预后因素,是免疫治疗的有前途的靶点。为了研究 TIL 是否对血管肉瘤患者的预后有任何影响,我们通过免疫组化染色 CD4、CD8、FOXP3 和 Ki67 对 55 名未经治疗的血管肉瘤患者(40 名处于 1 期的患者有皮肤局限性肿瘤,4 名处于 2 期的患者有淋巴结转移,11 名处于 3 期的患者有远处转移)进行了回顾性评估。Kaplan-Meier 法用于估计 1 期患者的总生存率。采用对数秩检验分析生存差异。与低值患者相比,原发肿瘤中 CD8(+)TIL 数量较高的患者存活时间明显更长。此外,TIL 中的 CD8 数量与无远处转移期呈正相关。3 期有远处转移的患者的原发 TIL(CD4 加 CD8)和 CD8(+)原发 TIL 的总数与其总生存率呈正相关。为了评估 CD8(+)效应 T 细胞是否被激活或分化,对外周血单核细胞(PBMC)进行了流式细胞术分析。与健康对照组(n=20)和晚期黑色素瘤患者(n=11)相比,血管肉瘤患者(n=10)的 PBMC 中产生 IFN-γ 的 CD8(+)T 细胞的百分比明显更高。这些结果表明,抗肿瘤免疫在血管肉瘤中具有临床相关性。

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