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结直肠癌肺转移灶中的肿瘤浸润淋巴细胞亚群和三级淋巴结构

Tumor-infiltrating lymphocyte subsets and tertiary lymphoid structures in pulmonary metastases from colorectal cancer.

作者信息

Schweiger Thomas, Berghoff Anna Sophie, Glogner Christoph, Glueck Olaf, Rajky Orsolya, Traxler Denise, Birner Peter, Preusser Matthias, Klepetko Walter, Hoetzenecker Konrad

机构信息

Division of Thoracic Surgery, Department of Thoracic Surgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.

Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Medical University of Vienna, Vienna, Austria.

出版信息

Clin Exp Metastasis. 2016 Oct;33(7):727-39. doi: 10.1007/s10585-016-9813-y. Epub 2016 Jul 23.

Abstract

The presence of tumor-infiltrating lymphocytes (TILs) and tertiary lymphoid structures (TLSs) reflects an active inflammatory tumor microenvironment. High density of TILs as well as presence of TLS is associated with improved survival in various solid cancer types. We aimed to describe the density and distribution of TILs and TLS in pulmonary metastases (PMs) from primary colorectal cancer (CRC) and its correlation with clinicopathological variables. Fifty-seven CRC pulmonary metastasectomy specimen (PM) and 31 matched primary CRC specimen were included. Cluster of differentiation (CD)3+, CD8+, CD45RO+ and FoxP3+ TILs were evaluated by immunohistochemistry and density was scored semiquantitatively. TLS were evaluated based on morphological criteria. Survival time was defined from pulmonary metastasectomy to death or last follow up. A marked infiltration with CD3+, CD8+, CD45RO+ and FoxP3+ TILs was evident in CRC PM and matched primary CRC. Further assessment of the immune infiltrate in PM showed that a high density of FOXP3+ TILs at the invasive margin [HR 2.40 (1.11-6.96); P = 0.031] and low density of CD8+ cells in TLS [HR 0.30 (0.14-0.79); P = 0.016] were associated with a worse prognosis in univariate analysis. Moreover, a low CD8/FoxP3-ratio of TILs at the invasive margin (P = 0.042) and in TLS (P = 0.027) conferred an impaired prognosis after pulmonary metastasectomy. Our findings suggest that CRC PM harbor an immune active microenvironment. The balance of CD8+ and FoxP3+ T-cells at the tumor border and in TLS provides prognostic information in patients with CRC PM.

摘要

肿瘤浸润淋巴细胞(TILs)和三级淋巴结构(TLSs)的存在反映了一种活跃的炎性肿瘤微环境。TILs的高密度以及TLS的存在与多种实体癌类型患者生存率的提高相关。我们旨在描述原发性结直肠癌(CRC)肺转移瘤(PMs)中TILs和TLS的密度及分布,并探讨其与临床病理变量的相关性。纳入了57例CRC肺转移瘤切除标本(PM)和31例匹配的原发性CRC标本。通过免疫组织化学评估分化簇(CD)3⁺、CD8⁺、CD45RO⁺和FoxP3⁺ TILs,并对密度进行半定量评分。根据形态学标准评估TLS。生存时间定义为从肺转移瘤切除至死亡或最后一次随访。在CRC肺转移瘤及匹配的原发性CRC中,CD3⁺、CD8⁺、CD45RO⁺和FoxP3⁺ TILs均有明显浸润。对肺转移瘤免疫浸润的进一步评估显示,在单因素分析中,侵袭边缘FOXP3⁺ TILs的高密度[风险比(HR)2.40(1.11 - 6.96);P = 0.031]和TLS中CD8⁺细胞的低密度[HR 0.30(0.14 - 0.79);P = 0.016]与较差的预后相关。此外,侵袭边缘(P = 0.042)和TLS中(P = 0.027)TILs的低CD8/FoxP3比值提示肺转移瘤切除术后预后不良。我们的研究结果表明,CRC肺转移瘤具有免疫活性微环境。肿瘤边界和TLS处CD8⁺和FoxP3⁺ T细胞的平衡为CRC肺转移瘤患者提供了预后信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b82/5035322/d03aafb284ee/10585_2016_9813_Fig1_HTML.jpg

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