Prognosis-related genes participate in immunotherapy of renal clear cell carcinoma possibly by targeting dendritic cells

被引:7
作者
Fang, Guodong [1 ]
Wang, Xudan [2 ]
机构
[1] Shaanxi Prov Peoples Hosp, Dept Pathol, Xian, Peoples R China
[2] Fourth Mil Med Univ, Xijing Hosp, Dept Hepatobiliary Surg, Xian, Peoples R China
来源
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY | 2022年 / 10卷
关键词
immunotherapy; prognosis; risk score; dendritic cell; clear cell renal cell carcinoma; PD-L1; IMMUNITY;
D O I
10.3389/fcell.2022.892616
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Tumor immunotherapy has become one of the most promising approaches to tumor treatment. This study aimed to screen genes involved in the response of clear cell renal cell carcinoma (ccRCC) to immunotherapy and analyze their function. Based on the Gene Expression Omnibus and The Cancer Genome Atlas datasets, we screened out nine differentially expressed genes (TYROBP, APOC1, CSTA, LY96, LAPTM5, CD300A, ALOX5, C1QA, and C1QB) associated with clinical traits and prognosis. A risk signature constructed by these nine genes could predict the survival probability for patients at 1 year, 3 years, and 5 years. The immune checkpoint blockade response rate in the high-risk group was significantly higher than in the low-risk group (49.25% vs. 24.72%, p & LE; 0.001). The nine prognosis-related genes were negatively correlated with activated dendritic cells in the low-risk group but not in the high-risk group. qRT-PCR, immunohistochemistry, and immunofluorescence showed that the nine prognosis-related genes were associated with dendritic cell activity and the PD-1 positive staining rate. In conclusion, the nine prognosis-related genes have a high prognostic value. The patients in the high-risk group were more likely to benefit from immunotherapy, and the mechanism might be related to the release of dendritic cell-mediated immunosuppression.
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页数:15
相关论文
共 26 条
[1]   Constitutive and acquired mechanisms of resistance to immune checkpoint blockade in human cancer [J].
Bellone, Matteo ;
Elia, Angela Rita .
CYTOKINE & GROWTH FACTOR REVIEWS, 2017, 36 :17-24
[2]   Beyond conventional immune-checkpoint inhibition - novel immunotherapies for renal cell carcinoma [J].
Braun, David A. ;
Bakouny, Ziad ;
Hirsch, Laure ;
Flippot, Ronan ;
Van Allen, Eliezer M. ;
Wu, Catherine J. ;
Choueiri, Toni K. .
NATURE REVIEWS CLINICAL ONCOLOGY, 2021, 18 (04) :199-214
[3]   The Immunotherapy Landscape in Renal Cell Carcinoma [J].
Brown, Landon C. ;
Desai, Kunal ;
Zhang, Tian ;
Ornstein, Moshe C. .
BIODRUGS, 2020, 34 (06) :733-748
[4]   Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden [J].
Chalmers, Zachary R. ;
Connelly, Caitlin F. ;
Fabrizio, David ;
Gay, Laurie ;
Ali, Siraj M. ;
Ennis, Riley ;
Schrock, Alexa ;
Campbell, Brittany ;
Shlien, Adam ;
Chmielecki, Juliann ;
Huang, Franklin ;
He, Yuting ;
Sun, James ;
Tabori, Uri ;
Kennedy, Mark ;
Lieber, Daniel S. ;
Roels, Steven ;
White, Jared ;
Otto, Geoffrey A. ;
Ross, Jeffrey S. ;
Garraway, Levi ;
Miller, Vincent A. ;
Stephens, Phillip J. ;
Frampton, Garrett M. .
GENOME MEDICINE, 2017, 9
[5]   Oncology Meets Immunology: The Cancer-Immunity Cycle [J].
Chen, Daniel S. ;
Mellman, Ira .
IMMUNITY, 2013, 39 (01) :1-10
[6]   Complement C1q (C1qA, C1qB, and C1qC) May Be a Potential Prognostic Factor and an Index of Tumor Microenvironment Remodeling in Osteosarcoma [J].
Chen, Long-hao ;
Liu, Jin-Fu ;
Yan-Lu ;
He, Xin-yu ;
Chi-Zhang ;
Zhou, Hong-hai .
FRONTIERS IN ONCOLOGY, 2021, 11
[7]  
Chen ML, 2018, INT J CLIN EXP PATHO, V11, P1431
[8]   Immunotherapy in Renal Cell Carcinoma: The Future Is Now [J].
Deleuze, Antoine ;
Saout, Judikael ;
Dugay, Frederic ;
Peyronnet, Benoit ;
Mathieu, Romain ;
Verhoest, Gregory ;
Bensalah, Karim ;
Crouzet, Laurence ;
Laguerre, Brigitte ;
Belaud-Rotureau, Marc-Antoine ;
Rioux-Leclercq, Nathalie ;
Kammerer-Jacquet, Solene-Florence .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2020, 21 (07)
[9]   Signatures of T cell dysfunction and exclusion predict cancer immunotherapy response [J].
Jiang, Peng ;
Gu, Shengqing ;
Pan, Deng ;
Fu, Jingxin ;
Sahu, Avinash ;
Hu, Xihao ;
Li, Ziyi ;
Traugh, Nicole ;
Bu, Xia ;
Li, Bo ;
Liu, Jun ;
Freeman, Gordon J. ;
Brown, Myles A. ;
Wucherpfennig, Kai W. ;
Liu, X. Shirley .
NATURE MEDICINE, 2018, 24 (10) :1550-+
[10]   CD11c+ dendritic cells and plasmacytoid DCs are activated by human cytomegalovirus and retain efficient T cell-stimulatory capability upon infection [J].
Kvale, EO ;
Dalgaard, J ;
Lund-Johansen, F ;
Rollag, H ;
Farkas, L ;
Midtvedt, K ;
Jahnsen, FL ;
Brinchmann, JE ;
Olweus, J .
BLOOD, 2006, 107 (05) :2022-2029