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 3

HIV+/ART-exp. tumor TCR repertoires are more similar to HIV– than HIV+/ART-naive.

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HIV+/ART-exp. tumor TCR repertoires are more similar to HIV– than HIV+/A...
(A) Distribution of unique productive tumor TCRs by HIV/ART status (n = 57). Most identified TCRs were found in a single HIV/ART group, with a considerable proportion of TCRs in both HIV+/ART-exp. and HIV– tumors. (B) Distribution of unique productive blood TCRs by HIV/ART status (n = 21). Most identified TCRs were found in a single HIV/ART group. (C) Tumor TCR repertoire overlap by HIV/ART status with reference to HIV+/ART-naive tumors (n = 57, pairwise Wilcoxon rank sum test). HIV+/ART-naive tumors have greater TCR repertoire overlap with HIV+/ART-exp. and HIV– tumors than each other. (D) Blood TCR repertoire overlap by HIV/ART status with reference to HIV+/ART-naive blood (n = 21, pairwise Wilcoxon rank sum test). Degree of blood TCR repertoire overlap was similar between HIV+/ART groups. (E) Number of unique TCRs found exclusively in ≥2 HIV+ tumor samples by ART status (n = 33, Wilcoxon rank sum test). There were few exclusively HIV+/ART-naive shared tumor TCRs. (F) Sample frequency of TCRs found exclusively in ≥2 HIV+ tumor samples by ART status (n = 33, Wilcoxon rank sum test). ART-naive tumors had higher frequencies of shared HIV+ exclusive TCRs also found in ART-exp. tumors compared with ART-exp. by Wilcoxon rank sum test. (G) Number of unique TCRs found exclusively in ≥2 HIV+ blood samples by ART status (n = 11). Most shared exclusively HIV+ blood TCRs were found in both ART-naive and ART-exp. (H) Sample frequency of TCRs found exclusively in ≥2 HIV+ blood samples (n = 11, Wilcoxon rank sum test). ART-naive and ART-exp. blood had similar levels of shared HIV+ TCRs found in both ART groups. Percentage of total unique tumor TCRs sequenced indicated in parentheses (A and B). Horizontal black line indicates median (D, F, and H).