The immune molecular landscape of the B7 and TNFR immunoregulatory ligand-receptor families in head and neck cancer: A comprehensive overview and the immunotherapeutic implications
The B7 family and tumor necrosis factor receptor (TNFR) superfamily play a vital role in the T-cell costimulatory and co-inhibitory pathways, regulating T-cell activation, tolerance, and exhaustion; therapeutic modulation of these pathways is translated into effective new cancer treatments. Better understanding of the immune molecular landscapes of the B7 and TNFR families would guide head and neck immuno-oncology clinical research. We performed comprehensive molecular profiling of 10 B7 and 6 TNFR family members in head and neck cancer. Over 20% of patients had B7 and TNFR gene alterations. B7 gene amplifications were relatively more common (3-11%) than TNFR gene amplifications (0-5%). Analysis of 496 sequenced samples revealed that all genes were upregulated: B7 and TNFR mRNA were upregulated in 158 cases (> 30%) and 83 cases (similar to 15%), respectively. B7-H1 (PD-L1) mRNA upregulation was the most common (similar to 10%). Promoter methylation analysis indicated an epigenetic basis for B7 and TNFR gene regulation (especially B7-H1, which was relatively strongly correlated with promoter methylation). B7-H1 expression was significantly associated with worse overall survival, and its expression was increased in cases with gene amplifications. Human papillomavirus (HPV) status correlated significantly with B7-H1 alterations at genetic level. Almost half (47.1%) of HPV-negative patients had deep or shallow B7-H1 deletion; >90% of HPV-positive patients had diploid, copy number gain, or amplification of B7-H1. This is the first study elucidating the immune molecular landscapes of the B7 and TNFR families in head and neck cancer, providing a potential novel rationale for clinical investigations.
基金:
National Science & Technology Pillar Program [2014BAI09B10]; Health & Medical Collaborative Innovation Project of Guangzhou City, China [201400000001]; Planned Science and Technology Project of Guangdong Province [2013B020400004]; Science and Technology Project of Guangzhou City, China [14570006]
语种:
外文
被引次数:
WOS:
中科院(CAS)分区:
出版当年[2017]版:
大类|1 区医学
小类|2 区免疫学2 区肿瘤学
最新[2023]版:
大类|2 区医学
小类|2 区免疫学2 区肿瘤学
第一作者:
第一作者机构:[1]Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol South China, Collaborat Innovat Ctr Canc Med, 651 Dongfeng Rd East, Guangzhou 510060, Guangdong, Peoples R China
通讯作者:
通讯机构:[1]Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol South China, Collaborat Innovat Ctr Canc Med, 651 Dongfeng Rd East, Guangzhou 510060, Guangdong, Peoples R China
推荐引用方式(GB/T 7714):
Chen Yu-Pei,Zhang Jian,Wang Ya-Qin,et al.The immune molecular landscape of the B7 and TNFR immunoregulatory ligand-receptor families in head and neck cancer: A comprehensive overview and the immunotherapeutic implications[J].ONCOIMMUNOLOGY.2017,6(3):-.doi:10.1080/2162402X.2017.1288329.
APA:
Chen, Yu-Pei,Zhang, Jian,Wang, Ya-Qin,Liu, Na,He, Qing-Mei...&Ma, Jun.(2017).The immune molecular landscape of the B7 and TNFR immunoregulatory ligand-receptor families in head and neck cancer: A comprehensive overview and the immunotherapeutic implications.ONCOIMMUNOLOGY,6,(3)
MLA:
Chen, Yu-Pei,et al."The immune molecular landscape of the B7 and TNFR immunoregulatory ligand-receptor families in head and neck cancer: A comprehensive overview and the immunotherapeutic implications".ONCOIMMUNOLOGY 6..3(2017):-