Specific HLA alleles, paired with TCR V- and J-gene segment usage, link to distinct multiple myeloma survival rates.

Multiple myeloma (MM) immunogenomics studies related to T-cell characterizations and involving large patient sets have been lacking, particularly in comparison to solid tumor types. Thus, we evaluated (i) HLA alleles, and (ii) T-Cell Receptor (TCR) V- and J-gene segment, HLA allele combinations, based on TCR recombinations in blood samples, for their potential associations with overall survival distinctions among an MM cohort. Two HLA alleles, and seven TCR V- or J-gene segment, HLA allele combinations were found to be associated with distinct overall survival rates. For examples, HLA-C*08:02, and the TRAV19, HLA-C*07:01 combination, were found to be associated with negative outcomes. In addition, anti-cytomegalovirus immune receptor sequences, from blood samples, were found to be associated with a positive outcome (p = 0.012, n = 278). These data, and other related immunogenomics data, indicate a potential opportunity to use personal immunogenetics parameters as guides to prognosis and therapies.

TRBV and TRBJ usage, when paired with specific HLA alleles, associates with distinct head and neck cancer survival rates.

Common or dominant, T-cell receptor (TCR), V and J usage, in combination with particular human leukocyte antigen (HLA) alleles, has been associated with differing outcomes in viral infections, autoimmunity, and more recently, in cancer. Cervical cancer in particular represents the most dramatic series of distinctions of outcomes associated with differing combinations of dominant V or J usage and HLA alleles, possibly because of the strong association of cervical cancer with human papilloma virus (HPV), in turn leading to a likely molecular consistency in the mechanism of HPV antigen presentation. Thus, we considered assessing TRB V and J usage, HLA allele combinations, for their associations with survival rates and related data, in the cancer genome atlas head and neck cancer dataset. We obtained the TRB VDJ recombination reads from both the blood and tumor exome files and determined the V and J identities. We then established case ID (patient) subsets of V or J usage, HLA alleles, and determined, for example, that the TRBJ2-7, HLA-B*40:01 combination was associated with a better disease free survival rate than were either the TRBJ1-3, HLA-DPB1*03:01 or the TRBJ2-1, HLA-DPB1*02:01 combinations. Furthermore, these analyses led to the conclusion that TRBJ1-5 usage, and the HLA-C*08:02 and HLA-DRB1*03:01 alleles, had independent associations with distinct overall survival rates. In sum, the results suggest that dominant V or J usage, HLA allele combinations, and in certain cases, dominant V or J usage independently of HLA, could be useful in prognosis and in guiding immunotherapies.