Comprehensive genomic and immunological characterization of Chinese non-small cell lung cancer patients

被引：171

作者：

Zhang, Xu-Chao ^{[1
,2
]}

Wang, Jun ^{[3
]}

Shao, Guo-Guang ^{[4
]}

Wang, Qun ^{[5
]}

Qu, Xiaotao ^{[6
]}

Wang, Bo ^{[6
]}

Moy, Christopher ^{[7
]}

Fan, Yue ^{[6
]}

Albertyn, Zayed ^{[8
]}

Huang, Xiayu ^{[6
]}

Zhang, Jingyu ^{[6
]}

Qiu, Yang ^{[6
]}

Platero, Suso ^{[7
]}

Lorenzi, Matthew V. ^{[7
]}

Zudaire, Enrique ^{[7
]}

Yang, Jennifer ^{[6
]}

Cheng, Ying ^{[9
]}

Xu, Lin ^{[10
]}

Wu, Yi-Long ^{[1
,2
]}

机构：

[1] Guangdong Prov Peoples Hosp, Guangdong Lung Canc Inst, Guangzhou 510080, Guangdong, Peoples R China

[2] Guangdong Acad Med Sci, Guangzhou 510080, Guangdong, Peoples R China

[3] Peking Univ, Peoples Hosp, Beijing 100044, Peoples R China

[4] Jilin Univ, Hosp 1, Thorac Surg, Changchun 130021, Jilin, Peoples R China

[5] Fudan Univ, Zhongshan Hosp, Shanghai 200032, Peoples R China

[6] Janssen R&D China, 355 Hong Qiao Rd, Shanghai 200030, Peoples R China

[7] Janssen R&D, 1400 McKean Rd, Spring House, PA 19002 USA

[8] Novocraft Technol, Petaling Jaya 46300, Selangor, Malaysia

[9] Jilin Prov Canc Hosp, Dept Med Oncol, Changchun 130012, Jilin, Peoples R China

[10] Nanjing Med Univ, Jiangsu Key Lab Mol & Translat Canc Res, Affiliated Canc Hosp, Dept Thorac Surg,Canc Inst Jiangsu Prov, Nanjing 210009, Jiangsu, Peoples R China

来源：

NATURE COMMUNICATIONS | 2019年 / 10卷 / 1期

关键词：

B-CELLS; CLINICOPATHOLOGICAL FEATURES; IMMUNE LANDSCAPE; MUTATIONS; HETEROGENEITY; ADENOCARCINOMAS; STATISTICS; EXPRESSION; RESPONSES; BLOCKADE;

D O I：

10.1038/s41467-019-09762-1

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Deep understanding of the genomic and immunological differences between Chinese and Western lung cancer patients is of great importance for target therapy selection and development for Chinese patients. Here we report an extensive molecular and immune profiling study of 245 Chinese patients with non-small cell lung cancer. Tumor-infiltrating lymphocyte estimated using immune cell signatures is found to be significantly higher in adenocarcinoma (ADC, 72.5%) compared with squamous cell carcinoma (SQCC, 54.4%). The correlation of genomic alterations with immune signatures reveals that low immune infiltration was associated with EGFR mutations in ADC samples, PI3K and/or WNT pathway activation in SQCC. While KRAS mutations are found to be significantly associated with T cell infiltration in ADC samples. The SQCC patients with high antigen presentation machinery and cytotoxic T cell signature scores are found to have a prolonged overall survival time.

引用

页数：12

共 60 条

[1] Signatures of mutational processes in human cancer [J].

Alexandrov, Ludmil B. ;

Nik-Zainal, Serena ;

Wedge, David C. ;

Aparicio, Samuel A. J. R. ;

Behjati, Sam ;

Biankin, Andrew V. ;

Bignell, Graham R. ;

Bolli, Niccolo ;

Borg, Ake ;

Borresen-Dale, Anne-Lise ;

Boyault, Sandrine ;

Burkhardt, Birgit ;

Butler, Adam P. ;

Caldas, Carlos ;

Davies, Helen R. ;

Desmedt, Christine ;

Eils, Roland ;

Eyfjord, Jorunn Erla ;

Foekens, John A. ;

Greaves, Mel ;

Hosoda, Fumie ;

Hutter, Barbara ;

Ilicic, Tomislav ;

Imbeaud, Sandrine ;

Imielinsk, Marcin ;

Jaeger, Natalie ;

Jones, David T. W. ;

Jones, David ;

Knappskog, Stian ;

Kool, Marcel ;

Lakhani, Sunil R. ;

Lopez-Otin, Carlos ;

Martin, Sancha ;

Munshi, Nikhil C. ;

Nakamura, Hiromi ;

Northcott, Paul A. ;

Pajic, Marina ;

Papaemmanuil, Elli ;

Paradiso, Angelo ;

Pearson, John V. ;

Puente, Xose S. ;

Raine, Keiran ;

Ramakrishna, Manasa ;

Richardson, Andrea L. ;

Richter, Julia ;

Rosenstiel, Philip ;

Schlesner, Matthias ;

Schumacher, Ton N. ;

Span, Paul N. ;

Teague, Jon W. .

NATURE, 2013, 500 (7463) :415-+

[2]

[Anonymous], COSMIC CATALOGUE SOM

[3] Immune Checkpoint Protein Inhibition for Cancer: Preclinical Justification for CTLA-4 and PD-1 Blockade and New Combinations [J].

Baksh, Kathryn ;

Weber, Jeffrey .

SEMINARS IN ONCOLOGY, 2015, 42 (03) :363-377

[4] Spatiotemporal Dynamics of Intratumoral Immune Cells Reveal the Immune Landscape in Human Cancer [J].

Bindea, Gabriela ;

Mlecnik, Bernhard ;

Tosolini, Marie ;

Kirilovsky, Amos ;

Waldner, Maximilian ;

Obenauf, Anna C. ;

Angell, Helen ;

Fredriksen, Tessa ;

Lafontaine, Lucie ;

Berger, Anne ;

Bruneval, Patrick ;

Fridman, Wolf Herman ;

Becker, Christoph ;

Pages, Franck ;

Speicher, Michael R. ;

Trajanoski, Zlatko ;

Galon, Jerome .

IMMUNITY, 2013, 39 (04) :782-795

[5] Safety and Activity of Anti-PD-L1 Antibody in Patients with Advanced Cancer [J].

Brahmer, Julie R. ;

Tykodi, Scott S. ;

Chow, Laura Q. M. ;

Hwu, Wen-Jen ;

Topalian, Suzanne L. ;

Hwu, Patrick ;

Drake, Charles G. ;

Camacho, Luis H. ;

Kauh, John ;

Odunsi, Kunle ;

Pitot, Henry C. ;

Hamid, Omid ;

Bhatia, Shailender ;

Martins, Renato ;

Eaton, Keith ;

Chen, Shuming ;

Salay, Theresa M. ;

Alaparthy, Suresh ;

Grosso, Joseph F. ;

Korman, Alan J. ;

Parker, Susan M. ;

Agrawal, Shruti ;

Goldberg, Stacie M. ;

Pardoll, Drew M. ;

Gupta, Ashok ;

Wigginton, Jon M. .

NEW ENGLAND JOURNAL OF MEDICINE, 2012, 366 (26) :2455-2465

[6] Antigen-Presenting Intratumoral B Cells Affect CD4+ TIL Phenotypes in Non-Small Cell Lung Cancer Patients [J].

Bruno, Tullia C. ;

Ebner, Peggy J. ;

Moore, Brandon L. ;

Squalls, Olivia G. ;

Waugh, Katherine A. ;

Eruslanov, Evgeniy B. ;

Singhal, Sunil ;

Mitchell, John D. ;

Franklin, Wilbur A. ;

Merrick, Daniel T. ;

McCarter, Martin D. ;

Palmer, Brent E. ;

Kern, Jeffrey A. ;

Slansky, Jill E. .

CANCER IMMUNOLOGY RESEARCH, 2017, 5 (10) :898-907

[7] B cells and professional APCs recruit regulatory T cells via CCL4 [J].

Bystry, RS ;

Aluvihare, V ;

Welch, KA ;

Kallikourdis, M ;

Betz, AG .

NATURE IMMUNOLOGY, 2001, 2 (12) :1126-1132

[8] Distinct patterns of somatic genome alterations in lung adenocarcinomas and squamous cell carcinomas [J].

Campbell, Joshua D. ;

Alexandrov, Anton ;

Kim, Jaegil ;

Wala, Jeremiah ;

Berger, Alice H. ;

Pedamallu, Chandra Sekhar ;

Shukla, Sachet A. ;

Guo, Guangwu ;

Brooks, Angela N. ;

Murray, Bradley A. ;

Imielinski, Marcin ;

Hu, Xin ;

Ling, Shiyun ;

Akbani, Rehan ;

Rosenberg, Mara ;

Cibulskis, Carrie ;

Ramachandran, Aruna ;

Collisson, Eric A. ;

Kwiatkowski, David J. ;

Lawrence, Michael S. ;

Weinstein, John N. ;

Verhaak, Roel G. W. ;

Wu, Catherine J. ;

Hammerman, Peter S. ;

Cherniack, Andrew D. ;

Getz, Gad ;

Artyomov, Maxim N. ;

Schreiber, Robert ;

Govindan, Ramaswamy ;

Meyerson, Matthew .

NATURE GENETICS, 2016, 48 (06) :607-+

[9] Cancer Statistics in China, 2015 [J].

Chen, Wanqing ;

Zheng, Rongshou ;

Baade, Peter D. ;

Zhang, Siwei ;

Zeng, Hongmei ;

Bray, Freddie ;

Jemal, Ahmedin ;

Yu, Xue Qin ;

He, Jie .

CA-A CANCER JOURNAL FOR CLINICIANS, 2016, 66 (02) :115-132

[10]

CHIN Y, 1992, ANTICANCER RES, V12, P1463

← 1 2 3 4 5 6 →