Herpes simplex virus lymphadenitis is associated with tumor reduction in a patient with chronic lymphocytic leukemia

• Type of Material: Article
• Authors: Andres Chang, Emory University; Anton M Sholukh, Fred Hutchinson Cancer Research Center; Andreas Wieland, Emory University; Mary Carrington, National Cancer Institute, Bethesda; David Jaye, Emory University; Meei-Li Huang, Fred Hutchinson Cancer Research Center; Hong Xie, Fred Hutchinson Cancer Research Center; Keith R Jerome, Fred Hutchinson Cancer Research Center; Pavitra Roychoudhury, Fred Hutchinson Cancer Research Center; Alexander L Greninger, Fred Hutchinson Cancer Research Center; Jean Koff, Emory University; Jonathon Cohen, Emory University; David M Koelle, Fred Hutchinson Cancer Research Center; Lawrence Corey, Fred Hutchinson Cancer Research Center; Christopher Flowers, Emory University; Rafi Ahmed, Emory University
• Language: English
• Date: 2022-09-15
• Publisher: AMER SOC CLINICAL INVESTIGATION INC
• Publication Version: Final Published Version
• Copyright Statement: © 2022 Chang et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1172/JCI161109
• Title of Journal or Parent Work: JOURNAL OF CLINICAL INVESTIGATION
• Volume: 132
• Issue: 18
• Grant/Funding Information: This work was supported by NIH grant 5U19AI057266; a Winship Cancer Institute Neil W. and William S. Elkin Fellowship (to AC); NIH T32 grant 4T32CA160040 (to AC); NIH contract 75N93019C00063 (to DMK); and the Emory Multiplexed Immunoassay Core, which is partly supported by Emory University and the National Center for Georgia Clinical and Translational Science Alliance of the NIH (award no. UL1TR002378).; This research was supported in part by the Intramural Research Program of the NIH, Frederick National Lab, Center for Cancer Research, under contract number HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the NIH or the Department of Health and Human Services.
• Keywords: Science & Technology; INFECTION; INTERFERON; BLOOD; SERIES; Medicine, Research & Experimental; RICHTER TRANSFORMATION; MEMORY; Research & Experimental Medicine; T-CELL RESPONSES; ASSAY; PROLIFERATION; Life Sciences & Biomedicine
• Research Categories: Health Sciences, Pathology; Health Sciences, Immunology; Biology, Microbiology

Abstract

BACKGROUND. Herpes simplex virus lymphadenitis (HSVL) is an unusual presentation of HSV reactivation in patients with chronic lymphocytic leukemia (CLL) and is characterized by systemic symptoms and no herpetic lesions. The immune responses during HSVL have not, to our knowledge, been studied. METHODS. Peripheral blood and lymph node (LN) samples were obtained from a patient with HSVL. HSV-2 viral load, antibody levels, B and T cell responses, cytokine levels, and tumor burden were measured. RESULTS. The patient showed HSV-2 viremia for at least 6 weeks. During this period, she had a robust HSV-specific antibody response with neutralizing and antibody-dependent cellular phagocytotic activity. Activated (HLA-DR+, CD38+) CD4+ and CD8+ T cells increased 18-fold, and HSV-specific CD8+ T cells in the blood were detected at higher numbers. HSV-specific B and T cell responses were also detected in the LN. Markedly elevated levels of proinflammatory cytokines in the blood were also observed. Surprisingly, a sustained decrease in CLL tumor burden without CLL-directed therapy was observed with this and also a prior episode of HSVL. CONCLUSION. HSVL should be considered part of the differential diagnosis in patients with CLL who present with signs and symptoms of aggressive lymphoma transformation. An interesting finding was the sustained tumor control after 2 episodes of HSVL in this patient. A possible explanation for the reduction in tumor burden may be that the HSV-specific response served as an adjuvant for the activation of tumor-specific or bystander T cells. Studies in additional patients with CLL are needed to confirm and extend these findings.