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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

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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 2

Increased tumor TCR repertoire clonality is associated with improved survival in HIV+ patients.

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Increased tumor TCR repertoire clonality is associated with improved sur...
(A) Kaplan-Meier curve of OS by HIV status (n = 62, Cox regression). Patients in this sequencing cohort had similar OS by HIV status. (B) Kaplan-Meier curve of OS by HIV/ART status (n = 62, Cox regression). HIV+/ART-naive patients trended toward improved OS compared with HIV+/ART-exp. in this sequencing cohort. (C) Kaplan-Meier curve of OS by tumor Simpson clonality (n = 35, Cox regression adjusted for age and HIV/ART status). Among all patients in the clonality data set, there was no statistically significant difference in OS by tumor Simpson clonality. (D) Kaplan-Meier curve depicting OS of HIV+ patients by tumor Simpson clonality (n = 23, Cox regression). Among HIV+ patients in the clonality data set, high tumor Simpson clonality was positively associated with OS. (E) Kaplan-Meier curve of OS of HIV– patients by tumor Simpson clonality (n = 12, Cox regression). Among HIV– patients in the clonality data set, there was no statistically significant difference in OS by tumor Simpson clonality. (F) Kaplan-Meier curve of OS by unique rearrangements in the blood (n = 17, Cox regression). Increased number of unique rearrangements in the blood was positively prognostic. High versus low as determined by median cutoff (C–F). Only productive templates were considered.

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