T-cell activation is associated with high-grade serous ovarian cancer survival

被引:9
作者
Wang, Lei [1 ]
Sun, Wenjie [2 ]
Zhang, Guoan [2 ]
Huo, Jingrui [2 ]
Tian, Yi [1 ]
Zhang, Yan [2 ]
Yang, Xiaohui [2 ]
Liu, Yingfu [3 ]
机构
[1] Cangzhou Med Coll, Microbiol & Immunol Dept, Cangzhou, Peoples R China
[2] Cangzhou Med Coll, Sci & Technol Expt Ctr, Cangzhou, Peoples R China
[3] Cangzhou Med Coll, Cangzhou Nanobody Technol Innovat Ctr, Cangzhou 061001, Peoples R China
关键词
CTLA4; high-grade serous ovarian cancer; overall survival; PD-1; T-cell activation; HEPATOCELLULAR-CARCINOMA; RISK SCORE; EXPRESSION; RECEPTORS; PD-1;
D O I
10.1111/jog.15234
中图分类号
R71 [妇产科学];
学科分类号
100211 ;
摘要
Aim High-grade serous ovarian cancer (HGSOC) is an aggressive disease that is largely resistant to today's immunotherapies. Here, we aimed to investigate the prognostic significance of CTLA4, PD-1, and T-cell activation status in HGSOC. Methods Using a publicly accessed microarray dataset including 260 HGSOC samples, we calculated Kaplan-Meier survival curves for overall survival (OS), evaluated associations with multivariate Cox regression models to evaluate the associations, and summarized using a hazard ratio (HR). The correlations between PD-1 gene expression and that of other genes were calculated by Pearson correlation. Results Multivariate survival analyses showed that high PD-1 expression but not CTLA4 was associated with longer OS (HR = 0.69; 95% confidence interval [CI] = 0.52-0.91; p = 0.01), and that higher T-cell activation score was associated with better outcome (HR = 0.74; 95% confidence interval [CI] = 0.58-0.95; p = 0.02). The top three PD-1 highly correlated genes were SIRPG (r = 0.90, p < 2E-16), FASL (r = 0.89, p < 2E-16), and CD8a (r = 0.87, p < 2E-16). HGSOC patients' OS is positively associated T-cell activation score and PD-1 expression but not CTLA4. Conclusion T cell activation score may serve as a candidate for personalized immunotherapy in HGSOC. The application of anti-PD-1 therapy to HGSOC should be cautious.
引用
收藏
页码:2189 / 2197
页数:9
相关论文
共 41 条
[1]   Lag-3, Tim-3, and TIGIT: Co-inhibitory Receptors with Specialized Functions in Immune Regulation [J].
Anderson, Ana C. ;
Joller, Nicole ;
Kuchroo, Vijay K. .
IMMUNITY, 2016, 44 (05) :989-1004
[2]   Costimulatory and Coinhibitory Receptor Pathways in Infectious Disease [J].
Attanasio, John ;
Wherry, E. John .
IMMUNITY, 2016, 44 (05) :1052-1068
[3]   Anti-PD-1/PD-L1 therapy of human cancer: past, present, and future [J].
Chen, Lieping ;
Han, Xue .
JOURNAL OF CLINICAL INVESTIGATION, 2015, 125 (09) :3384-3391
[4]   PD-1/PD-L1 expression and tumor-infiltrating lymphocytes are prognostically favorable in advanced high-grade serous ovarian carcinoma [J].
de la Fuente, Laura Martin ;
Westbom-Fremer, Sofia ;
Arildsen, Nicolai Skovbjerg ;
Hartman, Linda ;
Malander, Susanne ;
Kannisto, Paivi ;
Masback, Anna ;
Hedenfalk, Ingrid .
VIRCHOWS ARCHIV, 2020, 477 (01) :83-91
[5]   Prognostic and predictive role of CD8 and PD-L1 determination in lung tumor tissue of patients under anti-PD-1 therapy [J].
Fumet, Jean-David ;
Richard, Corentin ;
Ledys, Fanny ;
Klopfenstein, Quentin ;
Joubert, Philippe ;
Routy, Bertrand ;
Truntzer, Caroline ;
Gagne, Andreanne ;
Hamel, Marc-Andre ;
Guimaraes, Camila Figueiredo ;
Coudert, Bruno ;
Arnould, Laurent ;
Favier, Laure ;
Lagrange, Aurelie ;
Ladoire, Sylvain ;
Saintigny, Pierre ;
Ortiz-Cuaran, Sandra ;
Perol, Maurice ;
Foucher, Pascal ;
Hofman, Paul ;
Ilie, Marius ;
Chevrier, Sandy ;
Boidot, Romain ;
Derangere, Valentin ;
Ghiringhelli, Francois .
BRITISH JOURNAL OF CANCER, 2018, 119 (08) :950-960
[6]   Tumour gene expression signature in primary melanoma predicts long-term outcomes [J].
Garg, Manik ;
Couturier, Dominique-Laurent ;
Nsengimana, Jeremie ;
Fonseca, Nuno A. ;
Wongchenko, Matthew ;
Yan, Yibing ;
Lauss, Martin ;
Jonsson, Goeran B. ;
Newton-Bishop, Julia ;
Parkinson, Christine ;
Middleton, Mark R. ;
Bishop, D. Timothy ;
McDonald, Sarah ;
Stefanos, Nikki ;
Tadross, John ;
Vergara, Ismael A. ;
Lo, Serigne ;
Newell, Felicity ;
Wilmott, James S. ;
Thompson, John F. ;
Long, Georgina V. ;
Scolyer, Richard A. ;
Corrie, Pippa ;
Adams, David J. ;
Brazma, Alvis ;
Rabbie, Roy .
NATURE COMMUNICATIONS, 2021, 12 (01)
[7]   Identification of an immune gene expression signature associated with favorable clinical features in Treg-enriched patient tumor samples [J].
Givechian, Kevin B. ;
Wnuk, Kamil ;
Garner, Chad ;
Benz, Stephen ;
Garban, Hermes ;
Rabizadeh, Shahrooz ;
Niazi, Kayvan ;
Soon-Shiong, Patrick .
NPJ GENOMIC MEDICINE, 2018, 3
[8]   Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer [J].
Hamanishi, Junzo ;
Mandai, Masaki ;
Iwasaki, Masashi ;
Okazaki, Taku ;
Tanaka, Yoshimasa ;
Yamaguchi, Ken ;
Higuchi, Toshihiro ;
Yagi, Haruhiko ;
Takakura, Kenji ;
Minato, Nagahiro ;
Honjo, Tasuku ;
Fujii, Shingo .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (09) :3360-3365
[9]   Safety and Antitumor Activity of Anti-PD-1 Antibody, Nivolumab, in Patients With Platinum-Resistant Ovarian Cancer [J].
Hamanishi, Junzo ;
Mandai, Masaki ;
Ikeda, Takafumi ;
Minami, Manabu ;
Kawaguchi, Atsushi ;
Murayama, Toshinori ;
Kanai, Masashi ;
Mori, Yukiko ;
Matsumoto, Shigemi ;
Chikuma, Shunsuke ;
Matsumura, Noriomi ;
Abiko, Kaoru ;
Baba, Tsukasa ;
Yamaguchi, Ken ;
Ueda, Akihiko ;
Hosoe, Yuko ;
Morita, Satoshi ;
Yokode, Masayuki ;
Shimizu, Akira ;
Honjo, Tasuku ;
Konishi, Ikuo .
JOURNAL OF CLINICAL ONCOLOGY, 2015, 33 (34) :4015-+
[10]   High PD-1 expression level is associated with an unfavorable prognosis in patients with cervical adenocarcinoma [J].
Ishikawa, Masako ;
Nakayama, Kentaro ;
Nakamura, Kohei ;
Yamashita, Hitomi ;
Ishibashi, Tomoka ;
Minamoto, Toshiko ;
Lida, Kouji ;
Razia, Sultana ;
Ishikawa, Noriyoshi ;
Nakayama, Satoru ;
Otsuki, Yoshiro ;
Kyo, Satoru .
ARCHIVES OF GYNECOLOGY AND OBSTETRICS, 2020, 302 (01) :209-218