ABSTRACT
The B7 family and tumor necrosis factor receptor (TNFR) superfamily play a vital role in the T-cell co-stimulatory 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 (∼15%), respectively. B7-H1 (PD-L1) mRNA upregulation was the most common (∼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.
Disclosure of potential conflicts of interest
No potential conflicts of interest were disclosed.
Acknowledgments
We would like to thank the staff members of the Cancer Genome Atlas for their involvement in the cBioPortal for Cancer Genomics Program. We also thank the anonymous editors and reviewers for their insightful comments and great efforts to improve this manuscript.
Funding
This work was supported by grants from the National Science & Technology Pillar Program during the Twelfth Five-year Plan Period (2014BAI09B10); the Health & Medical Collaborative Innovation Project of Guangzhou City, China (201400000001); the Planned Science and Technology Project of Guangdong Province (2013B020400004); and the Science and Technology Project of Guangzhou City, China (14570006).