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肿瘤微环境相关因素与直肠癌新辅助治疗疗效及预后的相关性

Correlation between tumor microenvironment-associated factors and the efficacy and prognosis of neoadjuvant therapy for rectal cancer.

作者信息

Zhang Siyu, Bai Wenqi, Tong Xunan, Bu Peng, Xu Jing, Xi Yanfeng

机构信息

Department of Pathology, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.

Department of Colorectal Surgery, Shanxi Provincial Cancer Hospital, Taiyuan, Shanxi 030013, P.R. China.

出版信息

Oncol Lett. 2019 Jan;17(1):1062-1070. doi: 10.3892/ol.2018.9682. Epub 2018 Nov 9.

Abstract

The tumor microenvironment contributes to the survival and development of tumor cells and is therefore a key target for cancer therapy. The tumor microenvironment has unique physical and chemical properties and is associated with inflammation and immunity. To examine the correlation between tumor microenvironment-associated factors and the efficacy and prognosis of neoadjuvant therapy for rectal cancer, and to compare the differences between two treatments [neoadjuvant chemotherapy (NAC) vs. neoadjuvant chemoradiotherapy (NACR)], an immunohistochemical method was used to measure the expression levels of CD4 tumor-infiltrating lymphocytes (TILs), cluster of differentiation (CD)8TILs, forkhead box P3 (FOXP3)TILs, cytotoxic T lymphocyte-associated antigen-4TILs and programmed death ligand-1 (PD-L1)TILs in 109 patients with rectal cancer, pre- and post-neoadjuvant therapy. The significance of these protein expression patterns was also analyzed using tissue microarrays, and the prognostic significance of these findings evaluated. The results indicated that high levels of CD4TILs, CD8TILs and PD-L1TILs may be associated with favorable responses to neoadjuvant therapy, whereas high levels of FOXP3TILs were associated with poor therapeutic responses. Expression levels of CD8TILs and FOXP3TILs following neoadjuvant therapy were independent prognostic factors and affected the total survival of patients subjected to neoadjuvant therapy for the treatment of rectal cancer. Moreover, the effects of NAC and NACR on the tumor microenvironment may be different.

摘要

肿瘤微环境有助于肿瘤细胞的存活和发展,因此是癌症治疗的关键靶点。肿瘤微环境具有独特的物理和化学性质,并与炎症和免疫相关。为了研究肿瘤微环境相关因素与直肠癌新辅助治疗疗效及预后的相关性,并比较两种治疗方法[新辅助化疗(NAC)与新辅助放化疗(NACR)]之间的差异,采用免疫组织化学方法检测了109例直肠癌患者新辅助治疗前后肿瘤浸润淋巴细胞(TILs)中CD4、分化簇(CD)8、叉头框P3(FOXP3)、细胞毒性T淋巴细胞相关抗原4和程序性死亡配体1(PD-L1)的表达水平。还使用组织芯片分析了这些蛋白质表达模式的意义,并评估了这些发现的预后意义。结果表明,高水平的CD4 TILs、CD8 TILs和PD-L1 TILs可能与新辅助治疗的良好反应相关,而高水平的FOXP3 TILs则与不良治疗反应相关。新辅助治疗后CD8 TILs和FOXP3 TILs的表达水平是独立的预后因素,影响直肠癌新辅助治疗患者的总生存期。此外,NAC和NACR对肿瘤微环境的影响可能不同。

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