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细胞因子诱导的杀伤细胞治疗的肺鳞状细胞癌和腺癌中基因与浸润性免疫细胞的预后情况

The prognostic landscape of genes and infiltrating immune cells in cytokine induced killer cell treated-lung squamous cell carcinoma and adenocarcinoma.

作者信息

Wang Jian, Yang Fan, Sun Qian, Zeng Ziqing, Liu Min, Yu Wenwen, Zhang Peng, Yu Jinpu, Yang Lili, Zhang Xinwei, Ren Xiubao, Wei Feng

机构信息

Department of Immunology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Immunology and Biotherapy, Tianjin 300060, China.

Department of Biotherapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Immunology and Biotherapy, Tianjin 300060, China.

出版信息

Cancer Biol Med. 2021 Aug 30;18(4):1134-47. doi: 10.20892/j.issn.2095-3941.2021.0023.

Abstract

OBJECTIVE

Patients with non-small cell lung cancer (NSCLC) respond differently to cytokine-induced killer cell (CIK) treatment. Therefore, potential prognostic markers to identify patients who would benefit from CIK treatment must be elucidated. The current research aimed at identifying predictive prognostic markers for efficient CIK treatment of patients with NSCLC.

METHODS

Patients histologically diagnosed with NSCLC were enrolled from the Tianjin Medical University Cancer Institute and Hospital. We performed whole-exome sequencing (WES) on the tumor tissues and paired adjacent benign tissues collected from 50 patients with NSCLC, and RNA-seq on tumor tissues of 17 patients with NSCLC before CIK immunotherapy treatment. Multivariate Cox proportional hazard regression analysis was used to analyze the association between clinical parameters and prognostic relevance. WES and RNA-seq data between lung squamous cell carcinoma (SCC) and adenocarcinoma (Aden) were analyzed and compared.

RESULTS

The pathology subtype of lung cancer was the most significantly relevant clinical parameter associated with DFS, as analyzed by multivariate Cox proportional hazard regression ( = 0.031). The patients with lung SCC showed better CIK treatment efficacy and extended DFS after CIK treatment. Relatively low expression of HLA class II genes and checkpoint molecules, and less immunosuppressive immune cell infiltration were identified in the patients with lung SCC.

CONCLUSIONS

Coordinated suppression of the expression of HLA class II genes and checkpoint molecules, as well as less immune suppressive cell infiltration together contributed to the better CIK treatment efficacy in lung SCC than lung Aden.

摘要

目的

非小细胞肺癌(NSCLC)患者对细胞因子诱导的杀伤细胞(CIK)治疗反应各异。因此,必须阐明可识别能从CIK治疗中获益患者的潜在预后标志物。当前研究旨在确定NSCLC患者有效CIK治疗的预测性预后标志物。

方法

从天津医科大学肿瘤医院招募经组织学诊断为NSCLC的患者。我们对50例NSCLC患者的肿瘤组织及配对的相邻良性组织进行了全外显子测序(WES),并对17例NSCLC患者在CIK免疫治疗前的肿瘤组织进行了RNA测序。采用多变量Cox比例风险回归分析来分析临床参数与预后相关性之间的关联。对肺鳞状细胞癌(SCC)和腺癌(Aden)之间的WES和RNA测序数据进行了分析和比较。

结果

通过多变量Cox比例风险回归分析(P = 0.031),肺癌的病理亚型是与无病生存期(DFS)最显著相关的临床参数。肺SCC患者显示出更好的CIK治疗效果,且CIK治疗后DFS延长。在肺SCC患者中发现HLA II类基因和检查点分子的表达相对较低,免疫抑制性免疫细胞浸润较少。

结论

HLA II类基因和检查点分子表达的协同抑制,以及较少的免疫抑制细胞浸润共同导致肺SCC的CIK治疗效果优于肺腺癌。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be23/8610154/f0a037c5a036/cbm-18-1134-g001.jpg

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