Deciphering Microenvironment of NSCLC based on CD8+TIL Density and PD-1/PD-L1 Expression

被引:33
作者
Lin, Ziying [1 ,2 ]
Gu, Jincui [1 ]
Cui, Xiaoxian [1 ,2 ]
Huang, Lixia [1 ]
Li, Shaoli [1 ]
Feng, Jinlun [1 ,2 ]
Liu, Baomo [1 ,2 ]
Zhou, Yanbin [1 ]
机构
[1] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Resp Med, Guangzhou, Guangdong, Peoples R China
[2] Sun Yat Sen Univ, Zhongshan Sch Med, Guangzhou, Guangdong, Peoples R China
基金
中国国家自然科学基金;
关键词
non-small-cell lung cancer (NSCLC); programmed cell death-1 (PD-1); programmed cell death-ligand 1 (PD-L1); tumor microenvironment; survival; CELL LUNG-CANCER; MISMATCH REPAIR DEFICIENCY; CD8(+) T-CELLS; PD-L1; EXPRESSION; OPEN-LABEL; DOCETAXEL; BLOCKADE; PEMBROLIZUMAB; INFILTRATION; ATEZOLIZUMAB;
D O I
10.7150/jca.26444
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: To determine whether distinct tissue immune microenvironments differentially impact on clinical outcome in non-small cell lung cancer (NSCLC), an extended analysis of PD-1/PD-L1 and Tumor Infiltrating Lymphocytes (TILs) was performed. Materials and Methods: 1016 NSCLC mRNA-sequence samples from The Genome Data Analysis Center (TCGA) and 275 NSCLC mRNA-microarray samples from Gene Expression Omnibus (GEO)were included as testing cohort and validation cohort respectively. Enrichment scores of CD8+ T cells' metagene were used for quantifying its infiltrating density. Based on the median values of CD8+ T cell density and PD-1/PD-L1 mRNA expression, the samples were classified into four Tumor Immune Microenvironment types (TIMTs). Overall survival, as well as clinicopathological features, mutational profiles, mismatch repair score etc. were compared across the four types. Results: Neither PD-1 expression nor PD-L1 expression was associated with outcome in the overall NSCLC. Classification of TIMT based on PD-1/PD-L1 and CD8+ TIL could efficiently classify patients of different survival in ADC but not SCC, with the best overall survival achieved in TIMT3 (high CD8+ TIL and low PD-1/PD-L1), whereas TIMT2 (low CD8+ TIL and high PD-1/PD-L1) manifested the worst outcome. TIMT classification based on PD-1/CD8+ TIL could better stratify patient of different prognosis than PD-L1/CD8+ TIL based classification. EGFR wide type and IFN. overexpression were associated with TIMT4 (high PD-1/PD-L1 and high CD8+ TIL), whereas tumor mutational burden (TMB) manifested no significant difference across four TIMTs. Conclusion: The classification of tumors into four microenvironment subtypes based on PD-1/PD-L1 status and CD8+ TIL is an appropriate approach to stratify patients of different clinical outcome and better guide the practical use of immunotherapy.
引用
收藏
页码:211 / 222
页数:12
相关论文
共 48 条
[1]   IFN-γ from lymphocytes induces PD-L1 expression and promotes progression of ovarian cancer [J].
Abiko, K. ;
Matsumura, N. ;
Hamanishi, J. ;
Horikawa, N. ;
Murakami, R. ;
Yamaguchi, K. ;
Yoshioka, Y. ;
Baba, T. ;
Konishi, I. ;
Mandai, M. .
BRITISH JOURNAL OF CANCER, 2015, 112 (09) :1501-1509
[2]  
[Anonymous], 2018, CANC DISCOVERY
[3]  
[Anonymous], J CLIN ONCOL
[4]   Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer [J].
Borghaei, H. ;
Paz-Ares, L. ;
Horn, L. ;
Spigel, D. R. ;
Steins, M. ;
Ready, N. E. ;
Chow, L. Q. ;
Vokes, E. E. ;
Felip, E. ;
Holgado, E. ;
Barlesi, F. ;
Kohlhaeufl, M. ;
Arrieta, O. ;
Burgio, M. A. ;
Fayette, J. ;
Lena, H. ;
Poddubskaya, E. ;
Gerber, D. E. ;
Gettinger, S. N. ;
Rudin, C. M. ;
Rizvi, N. ;
Crino, L. ;
Blumenschein, G. R. ;
Antonia, S. J. ;
Dorange, C. ;
Harbison, C. T. ;
Finckenstein, F. Graf ;
Brahmer, J. R. .
NEW ENGLAND JOURNAL OF MEDICINE, 2015, 373 (17) :1627-1639
[5]   PD-L1 and PD-1 and characterization of tumor-infiltrating lymphocytes in high grade sarcomas of soft tissue - prognostic implications and rationale for immunotherapy [J].
Boxberg, Melanie ;
Steiger, Katja ;
Lenze, Ulrich ;
Rechl, Hans ;
von Eisenhart-Rothe, Ruediger ;
Woertler, Klaus ;
Weichert, Wilko ;
Langer, Rupert ;
Specht, Katja .
ONCOIMMUNOLOGY, 2018, 7 (03)
[6]   Neo-antigens predicted by tumor genome meta-analysis correlate with increased patient survival [J].
Brown, Scott D. ;
Warren, Rene L. ;
Gibb, Ewan A. ;
Martin, Spencer D. ;
Spinelli, John J. ;
Nelson, Brad H. ;
Holt, Robert A. .
GENOME RESEARCH, 2014, 24 (05) :743-750
[7]   KRAS mutation-induced upregulation of PD-L1 mediates immune escape in human lung adenocarcinoma [J].
Chen, Nan ;
Fang, Wenfeng ;
Lin, Zhong ;
Peng, Peijian ;
Wang, Juan ;
Zhan, Jianhua ;
Hong, Shaodong ;
Huang, Jiaxing ;
Liu, Lin ;
Sheng, Jin ;
Zhou, Ting ;
Chen, Ying ;
Zhang, Hongyu ;
Zhang, Li .
CANCER IMMUNOLOGY IMMUNOTHERAPY, 2017, 66 (09) :1175-1187
[8]   Genomic Analysis of Tumor Microenvironment Immune Types across 14 Solid Cancer Types: Immunotherapeutic Implications [J].
Chen, Yu-Pei ;
Zhang, Yu ;
Lv, Jia-Wei ;
Li, Ying-Qin ;
Wang, Ya-Qin ;
He, Qing-Mei ;
Yang, Xiao-Jing ;
Sun, Ying ;
Mao, Yan-Ping ;
Yun, Jing-Ping ;
Liu, Na ;
Ma, Jun .
THERANOSTICS, 2017, 7 (14) :3585-3594
[9]   Oncogenic RAS Signaling Promotes Tumor Immunoresistance by Stabilizing PD-L1 mRNA [J].
Coelho, Matthew A. ;
Trecesson, Sophie de Carne ;
Rana, Sareena ;
Zecchin, Davide ;
Moore, Christopher ;
Molina-Arcas, Miriam ;
East, Philip ;
Spencer-Dene, Bradley ;
Nye, Emma ;
Barnouin, Karin ;
Snijders, Ambrosius P. ;
Lai, Wi S. ;
Blackshear, Perry J. ;
Downward, Julian .
IMMUNITY, 2017, 47 (06) :1083-+
[10]   Classifying Non-Small Cell Lung Cancer by Status of Programmed Cell Death Ligand 1 and Tumor-Infiltrating Lymphocytes on Tumor Cells [J].
Cui, Shaohua ;
Dong, Lili ;
Qian, Jialin ;
Ye, Lin ;
Jiang, Liyan .
JOURNAL OF CANCER, 2018, 9 (01) :129-134