HIV infection and ART exposure impact tumor T-cell receptor repertoire of diffuse large B-cell lymphoma (2024)

¹Department of Pathology and Laboratory Medicine, School of Medicine, University of North Carolina, Chapel Hill, Chapel Hill, United States of America

²Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, United States of America

³University of North Carolina Project Malawi, Lilongwe, Malawi

⁴Department of Pathology, Kamuzu University of Health Sciences, Lilongwe, Malawi

⁵University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, United States of America

⁶National Cancer Institute Center for Global Health, Rockville, United States of America

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¹Department of Pathology and Laboratory Medicine, School of Medicine, University of North Carolina, Chapel Hill, Chapel Hill, United States of America

²Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, United States of America

³University of North Carolina Project Malawi, Lilongwe, Malawi

⁴Department of Pathology, Kamuzu University of Health Sciences, Lilongwe, Malawi

⁵University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, United States of America

⁶National Cancer Institute Center for Global Health, Rockville, United States of America

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¹Department of Pathology and Laboratory Medicine, School of Medicine, University of North Carolina, Chapel Hill, Chapel Hill, United States of America

²Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, United States of America

³University of North Carolina Project Malawi, Lilongwe, Malawi

⁴Department of Pathology, Kamuzu University of Health Sciences, Lilongwe, Malawi

⁵University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, United States of America

⁶National Cancer Institute Center for Global Health, Rockville, United States of America

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¹Department of Pathology and Laboratory Medicine, School of Medicine, University of North Carolina, Chapel Hill, Chapel Hill, United States of America

²Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, United States of America

³University of North Carolina Project Malawi, Lilongwe, Malawi

⁴Department of Pathology, Kamuzu University of Health Sciences, Lilongwe, Malawi

⁵University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, United States of America

⁶National Cancer Institute Center for Global Health, Rockville, United States of America

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¹Department of Pathology and Laboratory Medicine, School of Medicine, University of North Carolina, Chapel Hill, Chapel Hill, United States of America

²Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, United States of America

³University of North Carolina Project Malawi, Lilongwe, Malawi

⁴Department of Pathology, Kamuzu University of Health Sciences, Lilongwe, Malawi

⁵University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, United States of America

⁶National Cancer Institute Center for Global Health, Rockville, United States of America

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¹Department of Pathology and Laboratory Medicine, School of Medicine, University of North Carolina, Chapel Hill, Chapel Hill, United States of America

²Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, United States of America

³University of North Carolina Project Malawi, Lilongwe, Malawi

⁴Department of Pathology, Kamuzu University of Health Sciences, Lilongwe, Malawi

⁵University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, United States of America

⁶National Cancer Institute Center for Global Health, Rockville, United States of America

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¹Department of Pathology and Laboratory Medicine, School of Medicine, University of North Carolina, Chapel Hill, Chapel Hill, United States of America

²Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, United States of America

³University of North Carolina Project Malawi, Lilongwe, Malawi

⁴Department of Pathology, Kamuzu University of Health Sciences, Lilongwe, Malawi

⁵University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, United States of America

⁶National Cancer Institute Center for Global Health, Rockville, United States of America

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¹Department of Pathology and Laboratory Medicine, School of Medicine, University of North Carolina, Chapel Hill, Chapel Hill, United States of America

²Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, United States of America

³University of North Carolina Project Malawi, Lilongwe, Malawi

⁴Department of Pathology, Kamuzu University of Health Sciences, Lilongwe, Malawi

⁵University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, United States of America

⁶National Cancer Institute Center for Global Health, Rockville, United States of America

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¹Department of Pathology and Laboratory Medicine, School of Medicine, University of North Carolina, Chapel Hill, Chapel Hill, United States of America

²Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, United States of America

³University of North Carolina Project Malawi, Lilongwe, Malawi

⁴Department of Pathology, Kamuzu University of Health Sciences, Lilongwe, Malawi

⁵University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, United States of America

⁶National Cancer Institute Center for Global Health, Rockville, United States of America

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¹Department of Pathology and Laboratory Medicine, School of Medicine, University of North Carolina, Chapel Hill, Chapel Hill, United States of America

²Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, United States of America

³University of North Carolina Project Malawi, Lilongwe, Malawi

⁴Department of Pathology, Kamuzu University of Health Sciences, Lilongwe, Malawi

⁵University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, United States of America

⁶National Cancer Institute Center for Global Health, Rockville, United States of America

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¹Department of Pathology and Laboratory Medicine, School of Medicine, University of North Carolina, Chapel Hill, Chapel Hill, United States of America

²Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, United States of America

³University of North Carolina Project Malawi, Lilongwe, Malawi

⁴Department of Pathology, Kamuzu University of Health Sciences, Lilongwe, Malawi

⁵University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, United States of America

⁶National Cancer Institute Center for Global Health, Rockville, United States of America

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¹Department of Pathology and Laboratory Medicine, School of Medicine, University of North Carolina, Chapel Hill, Chapel Hill, United States of America

²Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, United States of America

³University of North Carolina Project Malawi, Lilongwe, Malawi

⁴Department of Pathology, Kamuzu University of Health Sciences, Lilongwe, Malawi

⁵University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, United States of America

⁶National Cancer Institute Center for Global Health, Rockville, United States of America

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¹Department of Pathology and Laboratory Medicine, School of Medicine, University of North Carolina, Chapel Hill, Chapel Hill, United States of America

²Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, United States of America

³University of North Carolina Project Malawi, Lilongwe, Malawi

⁴Department of Pathology, Kamuzu University of Health Sciences, Lilongwe, Malawi

⁵University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, United States of America

⁶National Cancer Institute Center for Global Health, Rockville, United States of America

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¹Department of Pathology and Laboratory Medicine, School of Medicine, University of North Carolina, Chapel Hill, Chapel Hill, United States of America

²Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, United States of America

³University of North Carolina Project Malawi, Lilongwe, Malawi

⁴Department of Pathology, Kamuzu University of Health Sciences, Lilongwe, Malawi

⁵University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, United States of America

⁶National Cancer Institute Center for Global Health, Rockville, United States of America

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¹Department of Pathology and Laboratory Medicine, School of Medicine, University of North Carolina, Chapel Hill, Chapel Hill, United States of America

²Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, United States of America

³University of North Carolina Project Malawi, Lilongwe, Malawi

⁴Department of Pathology, Kamuzu University of Health Sciences, Lilongwe, Malawi

⁵University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, United States of America

⁶National Cancer Institute Center for Global Health, Rockville, United States of America

Find articles byMerchant, A.in:JCI |PubMed |Google Scholar

¹Department of Pathology and Laboratory Medicine, School of Medicine, University of North Carolina, Chapel Hill, Chapel Hill, United States of America

²Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, United States of America

³University of North Carolina Project Malawi, Lilongwe, Malawi

⁴Department of Pathology, Kamuzu University of Health Sciences, Lilongwe, Malawi

⁵University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, United States of America

⁶National Cancer Institute Center for Global Health, Rockville, United States of America

Find articles byGopal, S.in:JCI |PubMed |Google Scholar

¹Department of Pathology and Laboratory Medicine, School of Medicine, University of North Carolina, Chapel Hill, Chapel Hill, United States of America

²Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, United States of America

³University of North Carolina Project Malawi, Lilongwe, Malawi

⁴Department of Pathology, Kamuzu University of Health Sciences, Lilongwe, Malawi

⁵University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, United States of America

⁶National Cancer Institute Center for Global Health, Rockville, United States of America

Find articles byFedoriw, Y.in:JCI |PubMed |Google Scholar

JCI Insight.https://doi.org/10.1172/jci.insight.180771.
Copyright © 2024, Roush et al.This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Abstract

The most common subtype of lymphoma globally, diffuse large B-cell lymphoma (DLBCL) is a leading cause of cancer death in people with HIV (HIV⁺). The restructuring of the T-cell compartment due to HIV infection and antiretroviral therapy (ART) may have implications for modern treatment selection, but current understanding of these dynamic interactions is limited. Here, we investigated the T-cell response to DLBCL by sequencing the T-cell receptor (TCR) repertoire in a cohort of HIV-negative (HIV^-), HIV⁺/ART^-experienced and HIV⁺/ART^-naïve DLBCL patients. HIV⁺/ART^-naïve tumor TCR repertoires were more clonal and more distinct from each other than HIV^- and HIV⁺/ART-experienced. Further, increased overlap between tumor and blood TCR repertoires was associated with improved survival and HIV/ART status. Our study describes TCR repertoire characteristics for the first time in an African DLBCL cohort and demonstrates contributions of HIV infection and ART exposure to the DLBCL TCR repertoire.

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