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癌巢中巨噬细胞和CD8(+) T细胞的主要浸润是IV期非小细胞肺癌患者生存的重要预测指标。

Predominant infiltration of macrophages and CD8(+) T Cells in cancer nests is a significant predictor of survival in stage IV nonsmall cell lung cancer.

作者信息

Kawai Osamu, Ishii Genichiro, Kubota Kaoru, Murata Yukinori, Naito Yoichi, Mizuno Tetsuya, Aokage Keiju, Saijo Nagahiro, Nishiwaki Yutaka, Gemma Akihiko, Kudoh Syoji, Ochiai Atsushi

机构信息

Pathology Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.

出版信息

Cancer. 2008 Sep 15;113(6):1387-95. doi: 10.1002/cncr.23712.

Abstract

BACKGROUND

The purpose of this study was to investigate whether tumor-infiltrating immune cells in biopsy specimens can be used to predict the clinical outcome of stage IV nonsmall cell lung cancer (NSCLC) patients.

METHOD

The authors performed an immunohistochemical study to identify and count the number of CD68(+) macrophages, c-kit(+) mast cells, and CD8(+) T cells in both cancer nests and cancer stroma in pretreatment biopsy specimens obtained from 199 patients with stage IV NSCLC treated by chemotherapy, and then analyzed for correlations between the number of immune cells and clinical outcome, including chemotherapy response and prognosis.

RESULTS

There was no correlation between the number of immune cells in either cancer nests or stroma and chemotherapy response. Patients with more tumor-infiltrating macrophages in cancer nests than in cancer stroma (macrophages, nests > stroma) had significantly better survival than nests < stroma cases median survival time (MST 440 days vs 199 days; P < .0001). Patients with more tumor-infiltrating CD8(+) T cells in cancer nests than in cancer stroma (CD8(+) T cells: nests > stroma) showed significantly better survival than in nests < stroma cases (MST 388 days vs 256 days; P = .0070). The proportion of tumor-infiltrating macrophages or CD8(+) T cells between cancer nests and stroma became independent prognostic factors in the multivariate analysis. Neither the number of mast cells in nests nor in stroma correlated with the clinical outcome.

CONCLUSIONS

Evaluation of the numbers of macrophages and CD8(+) T cells in cancer nests and stroma are useful biomarkers for predicting the prognosis of stage IV NSCLC patients treated with chemotherapy, but could fail to predict chemotherapy response.

摘要

背景

本研究旨在探讨活检标本中的肿瘤浸润免疫细胞是否可用于预测IV期非小细胞肺癌(NSCLC)患者的临床结局。

方法

作者进行了一项免疫组织化学研究,以识别和计数199例接受化疗的IV期NSCLC患者治疗前活检标本中癌巢和癌基质内CD68(+)巨噬细胞、c-kit(+)肥大细胞和CD8(+)T细胞的数量,然后分析免疫细胞数量与临床结局之间的相关性,包括化疗反应和预后。

结果

癌巢或基质中的免疫细胞数量与化疗反应之间无相关性。癌巢中肿瘤浸润巨噬细胞多于癌基质的患者(巨噬细胞,巢>基质)的生存期明显长于巢<基质的患者,中位生存期(MST)分别为440天和199天;P<.0001。癌巢中肿瘤浸润CD8(+)T细胞多于癌基质的患者(CD8(+)T细胞:巢>基质)的生存期明显长于巢<基质的患者(MST 388天对256天;P=.0070)。在多变量分析中,癌巢和基质之间肿瘤浸润巨噬细胞或CD8(+)T细胞的比例成为独立的预后因素。巢内或基质内肥大细胞的数量均与临床结局无关。

结论

评估癌巢和基质中巨噬细胞和CD8(+)T细胞的数量是预测接受化疗的IV期NSCLC患者预后的有用生物标志物,但无法预测化疗反应。

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