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

Arndt, Mary F.; Koohestani, Darush M.; Chobrutskiy, Boris I.; Mihyu, Moody M.; Diaz, Michael; Gozlan, Etienne C.; Yeagley, Michelle; Zaman, Saif; Roca, Andrea M.; Blanck, George

doi:10.1016/j.humimm.2020.08.007

Cited by 6 publications

(2 citation statements)

References 28 publications

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“…The presence of coding variation within the CDR3 of several novel alleles enabled the identification of these alleles in VDJdb, a curated database of published TCR CDR3s (43) TRB V and J usage was shown to be useful in guiding prognosis and immunotherapies in head and neck cancer cases, with dominant expression of specific V and J genes correlating with survival rates both in individuals with specific HLA allelic backgrounds and independent of HLA status (44). Intratumoral γδ T cells are the most favorable prognostic indicator in multiple cancers (45).…”

Section: Discussionmentioning

confidence: 99%

Archaic humans have contributed to large-scale variation in modern human T cell receptor genes

Corcoran

Chernyshev

Mandolesi

et al. 2022

Preprint

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The human T cell receptor (TCR) genes are critical for mediating immune responses to pathogens, tumors and regulating self-antigen recognition. A detailed analysis and validation of expressed TCR alpha, beta, gamma, and delta genes in 45 donors from 4 human populations: African, East Asian, South Asian, and European, revealed a total of 175 novel TCR variable and junctional alleles. The majority of novel alleles contained coding changes and were present at widely differing frequencies in the populations, a finding confirmed using DNA samples and sequences from the 1000 Genomes Project. Importantly, we identified three Neanderthal-derived, introgressed TCR regions, including a highly divergent novel TRGV4 variant, present in all archaic assemblies, that was frequent in all modern Eurasian population groups. Our results demonstrate significant variation in TCR genes at both individual and population levels, providing a strong incentive for including allelic variation in studies of TCR function in human biology.

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Section: Discussionmentioning

confidence: 99%

Archaic humans have contributed to large-scale variation in modern human T cell receptor genes

Corcoran

Chernyshev

Mandolesi

et al. 2022

Preprint

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“…And, for particular autoimmune and infectious diseases, certain combinations of TCR gene segment usage and HLA alleles predominate (Miles et al., 2010; Miles et al., 2011; Quandt et al., 2012). Recently, this has been shown to be the case for certain cancer survival probability distinctions as well (Arndt et al., 2020; Callahan, Tong, et al., 2018; Callahan, Yavorski, et al., 2018; Cios et al., 2022; Clark et al., 2019; Huda et al., 2021; Roca et al., 2019; Tong et al., 2019). Presumably or possibly, the association of specific TCR gene segment usage, HLA allele combinations with cancer outcomes is due to certain combinations representing either a better or worse opportunity to present cancer antigens, reflecting analogous presumptions for autoimmunity and infectious diseases.…”

Section: Introductionmentioning

confidence: 94%

TCR gene segment usage and HLA alleles that are associated with cancer survival rates also represent racial disparities

Angelakakis

Serraneau

Barker

et al. 2022

Int J Immunogenetics

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Understanding racial disparities in cancer outcomes continues to be a challenge, with likely many factors at play, including socioeconomic factors and genetic polymorphisms impacting basic cellular and molecular functions. Additionally, it is possible that specific combinations of environment and genetics have specific impacts. T‐cell receptor (TCR) gene segment usage, HLA allele combinations have been associated with autoimmune and infectious disease courses, and more recently, TCR gene segment usage, HLA allele combinations have been associated with distinct survival outcomes in cancer as well. We examined several such, previously reported cancer‐related TCR gene segment usage, HLA allele combinations for evidence of racial disparities, with regard to the prevalence of the combination in different racial groups. Results indicated that TCR gene segment usage, potentially reflecting environmental factors related to previous pathogen exposure, in combination with certain HLA alleles or independently, may represent a novel explanation for racial disparities in cancer outcomes. Overall, at this point, a genetic connection to racial disparities in cancer outcomes is detectable but remains modest, suggesting that other factors, such as socioeconomic factors, remain as important considerations.

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Archaic humans have contributed to large-scale variation in modern human T cell receptor genes

et al. 2023

View full text Add to dashboard Cite

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

Cited by 6 publications

References 28 publications

Archaic humans have contributed to large-scale variation in modern human T cell receptor genes

Archaic humans have contributed to large-scale variation in modern human T cell receptor genes

TCR gene segment usage and HLA alleles that are associated with cancer survival rates also represent racial disparities

Archaic humans have contributed to large-scale variation in modern human T cell receptor genes

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