Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 May 13;13(5):e011441.
doi: 10.1136/jitc-2024-011441.

Regional distribution of HLA frequencies in the USA: implications for TCR-based therapies

Christian Roy  1 , Tomasz Sewastianik  2 , Ileana Saenz  2 , Gregory J Opiteck  2 , Sean Stagg  3 , Martin Maiers  3 , Dirk Nagorsen  2
Affiliations

Regional distribution of HLA frequencies in the USA: implications for TCR-based therapies

Christian Roy et al. J Immunother Cancer. .

Abstract

Understanding regional distribution of HLA frequencies is crucial for optimizing enrollment in HLA-restricted clinical trials and to promote trial diversity per the Food and Drug Administration's 2020 mandate. Using US HLA frequency data and census demographics we developed a method to create high-resolution HLA class 1 genotypic frequency maps. Analyzing HLA-A*11:01 and HLA-B*58:01 as alleles of interest, we found significant US regional variations. HLA-A*11:01, which presents KRAS neoantigen mutations targeted by TCR T-cell therapies, showed 10-15% genotypic frequency (national average 11.2%), with western US states 1.5 times higher than average and local variations within California (10-19%). These insights can be used to guide clinical trial site selection, for example, in National Cancer Institute (NCI) cancer center catchment areas. For HLA-B*58:01, which reacts pharmacogenetically with allopurinol and results in severe cutaneous adverse reactions, Mississippi had a high frequency among US states, which could be used to guide potential public safety campaigns. This method can identify regions with high HLA type representation, aiding efficient patient identification and enrollment for HLA-specific clinical trials and health-awareness efforts.

Keywords: Adoptive cell therapy - ACT; Genetic; Human leukocyte antigen - HLA; Major histocompatibility complex - MHC; T cell Receptor - TCR.

PubMed Disclaimer

Conflict of interest statement

Competing interests: This study is sponsored by Affini-T Therapeutics. The authors are fully responsible for all content and editorial decisions, were involved in all stages of publication development, and have approved the final version. Corresponding author‘s email address: Christian.roy@affinittx.com

Figures

Figure 1
Figure 1
(A) Population-adjusted HLA-A*11:01 frequencies by continental US state. (B) Population-adjusted genotypic frequencies for HLA-A*11:01 by US county. (C) Correlation scatter plots comparing population-adjusted genotypic frequencies for HLA-A11:01, A02:01, and A*03:01 to geographically matched frequency data from the National Marrow Donor Program. Importantly, only counties or hexagons with ≥500 people were included. Spearman correlation (p) and Pearson Correlation (r) shown for each. (D) Population-adjusted genotypic frequencies for HLA-A*11:01 by CA county. (E) Population-adjusted genotypic frequencies for HLA-A*11:01 by H3:h4 hexagon within CA boundaries. (F) Population-adjusted genotypic frequencies by NCI catchment areas for HLA-A*11:01. CA, California; GF, genotypic frequency.
Figure 2
Figure 2
(A) Population-adjusted genotypic frequencies for HLA-B*58:01 by US county. (B) Population-adjusted genotypic frequencies for HLA-B*58:01 by MS county. (C) Population-adjusted genotypic frequencies for HLA-B*58:01 by H3:h4 hexagon within MS boundaries. (D) Population-adjusted genotypic frequencies by NCI catchment areas for HLA-B*58:01. GF, genotypic frequency; NCI, National Cancer Institute; MS, Mississippi.
See this image and copyright information in PMC

References

    1. Li J, Zhang Y, Fu T, et al. Clinical advances and challenges associated with TCR-T cell therapy for cancer treatment. Front Immunol 2024;15:1487782. 10.3389/fimmu.2024.1487782 - DOI - PMC - PubMed
    1. Wilson MR, Beachy SH, Schumm SN, eds. Committee on the use of race and ethnicity in biomedical research, board on health sciences policy, board on population health and public health practice, board on health care services, health and medicine division, national academies of sciences, engineering, and medicine. In: Rethinking race and ethnicity in biomedical research. Washington, D.C: National Academies Press, March 25, 2025: 27913. Available: https://nap.nationalacademies.org/catalog/27913
    1. Nasiri F, Safarzadeh Kozani P, Salem F, et al. Mechanisms of antigen-dependent resistance to chimeric antigen receptor (CAR)-T cell therapies. Cancer Cell Int 2025;25:64. 10.1186/s12935-025-03697-y - DOI - PMC - PubMed
    1. Roy C. T Cell Receptor Trials on Clinicaltrials.Gov as of 2025-03-014. Zenodo 2025.
    1. Meyer M, Mahr A, Brewer J, et al. A call to adapt the regulation of HLA testing for T cell receptor-based therapeutics. Nat Rev Drug Discov 2024;23:1–2. 10.1038/d41573-023-00189-4 - DOI - PubMed