T-cell receptor V and J usage paired with specific HLA alleles associates with distinct cervical cancer survival rates

Abstract

Cervical cancer is more strongly associated with a specific virus, Human Papilloma Virus (HPV), in otherwise healthy individuals, than is any other cancer. Thus, there is an expectation that an adaptive immune signature of cervical cancer would be highly apparent. Here we used a genomics approach to investigate the relationship between T-cell receptor (TCR) V and J usage and survival for patients diagnosed with cervical cancer, relying exclusively on tissue and blood exome files. Specific TCR V or J segments, identified in recombination reads recovered from the exome files, were combined with the patient HLA alleles to identify V or J, HLA allele combination groups associated with distinct survival rates. For examples, the T-cell receptor-β (TRB) V6-5, HLA-A*02:01 combination was associated with a positive outcome, and the TRBV6-1, HLA-A*01:01 combination was associated with a negative outcome. Overall, these results point to V or J usage, HLA allele combinations as survival biomarkers, likely conveniently accessible with a noninvasive procedure, and the results may point the way towards immunological reagents useful in therapy designs.