HIV infection and ART exposure affect tumor TCR repertoire of diffuse large B cell lymphoma
Sophia M. Roush, Jenny Coelho, Alexander M. Xu, Kaushik Puranam, Marriam Mponda, Edwards Kasonkanji, Maurice Mulenga, Tamiwe Tomoka, Jonathan Galeotti, Amy Brownlee, Hormas Ghadially, Maganizo Chagomerana, Blossom Damania, Matthew Painschab, Akil Merchant, Satish Gopal, Yuri Fedoriw
Sophia M. Roush, Jenny Coelho, Alexander M. Xu, Kaushik Puranam, Marriam Mponda, Edwards Kasonkanji, Maurice Mulenga, Tamiwe Tomoka, Jonathan Galeotti, Amy Brownlee, Hormas Ghadially, Maganizo Chagomerana, Blossom Damania, Matthew Painschab, Akil Merchant, Satish Gopal, Yuri Fedoriw
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Research Article AIDS/HIV Hematology

HIV infection and ART exposure affect tumor TCR repertoire of diffuse large B cell lymphoma

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. The restructuring of the T cell compartment because of 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-naive patients with DLBCL. HIV+/ART-naive tumor TCR repertoires were more clonal and more distinct from each other than HIV– and HIV+/ART-experienced ones. 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 to our knowledge in an African DLBCL cohort and demonstrates contributions of HIV infection and ART exposure to the DLBCL TCR repertoire.

Authors

Sophia M. Roush, Jenny Coelho, Alexander M. Xu, Kaushik Puranam, Marriam Mponda, Edwards Kasonkanji, Maurice Mulenga, Tamiwe Tomoka, Jonathan Galeotti, Amy Brownlee, Hormas Ghadially, Maganizo Chagomerana, Blossom Damania, Matthew Painschab, Akil Merchant, Satish Gopal, Yuri Fedoriw

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Figure 1

HIV/ART status is associated with tumor, but not blood, TCR repertoire bulk clonality metrics.

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HIV/ART status is associated with tumor, but not blood, TCR repertoire b...
(A) Simpson clonality by tissue type (n = 52, Wilcoxon rank sum test). Blood TCR repertoires had higher Simpson clonality compared with tumor. (B) Unique rearrangements by tissue type (n = 52, Wilcoxon rank sum test). Tumor TCR repertoires had more unique rearrangements compared with blood. (C) Relative abundance of TCRs with specific frequencies by sample type (n = 52, Wilcoxon rank sum test). Blood TCR repertoires had more hyperexpanded clones and small expansions compared with tumor, while tumor TCR repertoires had more large expansions. (D) Tumor Simpson clonality by HIV/ART status (n = 35, pairwise Wilcoxon rank sum test). HIV+/ART-naive tumor repertoires were more clonal compared with HIV+/ART-exp. and HIV–. (E) Tumor unique rearrangements by HIV/ART status (n = 35, pairwise Wilcoxon rank sum test). HIV+/ART-naive tumor repertoires had fewer unique rearrangements compared with HIV+/ART-exp. and HIV–. (F) Relative abundance of tumor TCRs with specific frequencies by HIV/ART status (n = 35, Kruskal-Wallis test). HIV+/ART-naive tumor TCR repertoires had more hyperexpanded clones. (G) Blood Simpson clonality by HIV/ART status (n = 17, pairwise Wilcoxon rank sum test). Similar blood TCR repertoire clonality among HIV/ART groups. (H) Blood unique rearrangements by HIV/ART status (n = 17, pairwise Wilcoxon rank sum test). Similar blood TCR repertoire diversity among HIV/ART groups. (I) Relative abundance of blood TCRs with specific frequencies by HIV/ART status (n = 17, Kruskal-Wallis test). Only productive templates were considered. Box plots show the interquartile range, median (line), and minimum and maximum (whiskers). DS indicates metrics were downsampled (A, B, D, and E). Horizontal black line indicates median (A, B, D, E, G, and H).