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. 2022 Oct;59(4):183-191.
doi: 10.1053/j.seminhematol.2022.11.002. Epub 2022 Dec 1.

The role of viruses in HIV-associated lymphomas

Kathryn Lurain  1 , Ramya Ramaswami  2 , Robert Yarchoan  2
Affiliations

The role of viruses in HIV-associated lymphomas

Kathryn Lurain et al. Semin Hematol. 2022 Oct.

Abstract

Lymphomas are among the most common cancers in people with HIV (PWH). The lymphoma subtypes and pathogenesis of lymphoma in PWH are different from the immunocompetent population. It is well-known that HIV causes severe CD4+ T cell lymphopenia in the absence of antiretroviral therapy (ART); however, the risk of developing certain subtypes of lymphoma remains elevated even in people receiving ART with preserved CD4+ T cells. HIV contributes to lymphomagenesis and causes decreased immune surveillance via T cell depletion and dysregulation, B cell dysregulation, and the potential contribution of HIV-encoded proteins. The oncogenic gammaherpesviruses, Epstein-Barr virus (EBV) and Kaposi sarcoma herpesvirus (KSHV, also known as human herpesvirus 8), are the causative agents in the majority of HIV-associated lymphomas. HIV-associated T cell depletion and dysregulation allows EBV and KSHV to proliferate in infected B cells. Specific EBV- and KSHV-encoded proteins participate in B cell activation, and proliferation leading to B cell transformation. Understanding the distinct pathogenesis of HIV-associated lymphomas affords opportunities to develop therapies that specifically target these unique aspects and improve lymphoma outcomes in PWH. Agents being studied that target the specific roles of HIV, EBV, and KSHV in lymphomagenesis include immunotherapies, targeted agents, and cellular therapies.

Keywords: AIDS; Epstein-barr virus; HIV; Human herpesvirus 8; Kaposi sarcoma herpesvirus; Lymphoma.

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Conflict of interest statement

Conflicts of Interest KL, RY, and RR report receiving research support from Bristol Myers Squibb through CRADAs with the NCI and receiving drugs for clinical trials from Merck, EMD-Serono, Eli Lilly, and CTI BioPharma through CRADAs with the NCI. RY reports receiving drug supply for laboratory research from Janssen Pharmaceuticals. RY is a co-inventor on US Patent 10,001,483 entitled "Methods for the treatment of Kaposi's sarcoma or KSHV-induced lymphoma using immunomodulatory compounds and uses of biomarkers." An immediate family member of RY is a co-inventor on patents or patent applications related to internalization of target receptors, epigenetic analysis, and ephrin tyrosine kinase inhibitors. All rights, title, and interest to these patents have been assigned to the U.S. Department of Health and Human Services; the government conveys a portion of the royalties it receives to its employee inventors under the Federal Technology Transfer Act of 1986 (P.L. 99-502).

Figures

Figure 1.
Figure 1.. Subtypes and characteristics of HIV-associated lymphomas
HIV-associated lymphomas are comprised of a heterogeneous group of non-Hodgkin lymphomas (Burkitt lymphoma [BL], germinal center-like diffuse large B cell lymphoma [GcB-DLBCL], activated B cell-like DLBCL [ABC-DLBCL], primary central nervous system lymphoma [PCNSL], plasmablastic lymphoma [PBL], and primary effusion lymphoma [PEL]) and classical Hodgkin lymphoma (HL). The level of HIV-associated immune suppression plays a role in the development of various subtypes and the advent of antiretroviral therapy (ART) has had varying effects on the incidence of the various subtypes. Over time survival has improved for all subtypes, but those rare subtypes associated with significant immune suppression, such as PBL and PEL, still have poorer outcomes comparatively. Epstein-Barr virus (EBV) and Kaposi sarcoma herpesvirus (KSHV) play large roles in the pathogenesis of HIV-associated lymphomas. The EBV latency pattern (LP) determines the oncogenic pathways dysregulated in EBV+ lymphomas. This figure was created on biorender.com.
Figure 2.
Figure 2.. Proposed effects of HIV, Epstein-Barr virus, and Kaposi sarcoma herpesvirus on lymphomagenesis
HIV, Epstein-Barr virus (EBV), and Kaposi sarcoma herpesvirus (KSHV) have significant effects on lymphomagenesis through depletion of T cells but also through activation and transformation of B cells via chronic antigen stimulation, cytokine dysfunction, and through possible actions of specific viral oncoproteins. KSHV-encoded proteins are marked with an asterisk. This figure was created on biorender.com
See this image and copyright information in PMC

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