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

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

“…Thus, the racial disparity indicated by HLA-B*27:05 was not consistent with the worse OS observed in "Blacks." In a previous study, the TRAV1-2 gene segment had a better OS outcome (p = .0219) compared to all remaining TCR gene segments (Huda et al, 2021). Analysis for this report revealed that 9.66% of "Blacks" represented TRAV1-2, whereas "Blacks" consisted of 19.0% of the entire MMRF dataset (p = .0073).…”

“…Thus, the underrepresentation of "Blacks" among the HLA-DQB1*06:03 allele group of cases was consistent with a worse OS outcome for "Blacks." By contrast, while the HLA-B*27:05 allele correlated with a worse OS (p = .0222) compared to all remaining HLA allele types represented by all of the remaining MMRF cases (Huda et al, 2021), the proportion of "Blacks" in the HLA-B*27:05 allele population was underrepresented (2.13%) compared to the proportion of "Blacks" in the entire MMRF population (13.8%; two-proportion test, p = .0214) (Table 4; Table S3). Thus, the racial disparity indicated by HLA-B*27:05 was not consistent with the worse OS observed in "Blacks."…”

“…To investigate possible racial disparities for the TCR gene segment, HLA allele combinations associated with distinct cancer survival outcomes, we obtained the TCGA case IDs for these associations from previous publications (Callahan, Tong, et al., 2018; Callahan, Yavorski, et al., 2018; Huda et al., 2021). In addition, using the clinical data from cbioportal.org, for each type of cancer, we obtained the racial proportions for each TCR gene segment usage, HLA allele combination.…”

“…Keeping in mind the relative uniqueness of the MMRF data with regard to a worse OS for "Blacks" (in comparison to the other studies discussed in the paragraph above), analysis of the MMRF dataset revealed two OS-related HLA alleles and one OS-related TRAV gene segment that were also representative of racial differences, for "Blacks" and "non-Blacks." To begin consideration of the results of this report, note that in an earlier study, the HLA-DQB1*06:03 allele represented a better OS outcome (p = .0344) compared to all remaining HLA allele types when evaluating the entire MMRF dataset (Huda et al, 2021). In the subsequent analyses for this report, 2.72% of "Blacks" represented the HLA-DQB1*06:03 allele, whereas "Blacks" represented 13.8% of the entire dataset (two-proportion test, p = .001) (Table 4; Table S3).…”

“…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.…”