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 4

Overlap of tumor and blood TCR repertoires associates with HIV/ART status and survival.

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Overlap of tumor and blood TCR repertoires associates with HIV/ART statu...
(A) TCRs shared by at least 5 tumor samples that associated with overall (blue) and/or progression-free (yellow) survival by univariate Cox regression. (B) TCRs shared by at least 5 blood samples that associated with overall (blue) and/or progression-free (yellow) survival by univariate Cox regression. (C) Frequency of tumor TCRs found in blood for patients with matched tumor and blood samples by age (n = 16, Spearman correlation). Age negatively associated with frequency of tumor TCRs in blood. (D) Frequency of tumor TCRs found in blood for patients with matched tumor and blood samples by HIV/ART status (n = 16, pairwise Wilcoxon rank sum test). HIV+/ART-naive patients had higher tumor-blood overlap compared with HIV– patients. Horizontal black line indicates median. (E) Kaplan-Meier curve of overall survival probability by tumor-blood TCR repertoire overlap (n = 16, Cox regression). Patients with higher tumor-blood overlap had improved survival compared with those with low overlap. Median cutoff was used to determine high versus low overlap.