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Christopher R. Flowers, Chair, Professor, Department of Lymphoma/Myeloma, MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 429 Houston, Texas 77030, USA. Phone: 713.745.6095; Email: crflowers@mdanderson.org

Rafi Ahmed, Director, Emory Vaccine Center, Georgia Research Alliance Eminent Scholar, Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA. Phone: 404.727.4700; Email: rahmed@emory.edu

AC conceptualized the study, designed and performed the experiments, performed the clinical data abstraction, provided patient samples, analyzed the results, generated the figures, and wrote the manuscript. AMS designed and performed experiments, analyzed the results, generated the figures, and wrote the manuscript. AW, DLJ, MC, MLH, and HX performed the experiments. KRJ, PR, and ALG performed experiments and analyzed the results. JLK, and JBC provided patient samples and clinical support, analyzed the data, and contributed to writing of the manuscript. DMK, LC, CRF, and RA conceptualized the study, analyzed the data, provided funding, and wrote the manuscript.

We thank Hong Wu, Blake Hagen, Kathleen Luu, and Alvason Li for technical assistance; Mindy Miner for technical editing; the Winship Cancer Institute (WCI) Lymphoma Program clinical research team for sample acquisition; and the patient for participating in this study.

ALG reports contract testing remunerations from Abbott, Cepheid, Novavax, Pfizer, and Hologic and research support from Gilead and Merck. DMK reports grant support from Sanofi Pasteur related to an HSV-2 vaccine, is a member of the scientific advisory boards for Curevo Vaccine and MaxHealth LLC, and is a co-inventor of institutionally owned patents on HSV-2 vaccines and virus-specific T cell receptors (US patent nos. 6,375,952; 6,413,518; 6,814,969; 6,855,317; 6,962,709; 7,037,509; 7,078,041; 7,431,934; 7,628,993; 7,666,434; 7,744,903; 7,897,339; 7,935,352; 8,067,010; 8,197,824; 8,263,087; 8,293,248; 8,460,674; 8,828,408; 8,834,894; 8,840,903; 8,840,904; 8,852,602; 8,852,610; 8,852,611; 9,044,447; 9,138,473; 9,161,973; 9,205,146; 9,328,144; 9,579,376; 9,675,688). JBC is a member of the advisory board for Aptitude Health, Janssen, BeiGene, Kite/Gilead, Astra Zeneca, and Loxo/Lilly. He also receives research funding from BioInvent, Genentech, BMS/Celgene, Takeda, Novartis, and Loxo/Lilly. CRF is a consultant for AstraZeneca, Bayer, BeiGene, BioAscend, Bristol Myers Squibb, Celgene, Curio Sciences, Denovo Biopharma, Epizyme/Incyte, Foresight Diagnostics, Genentech/Roche, Genmab, MEI Pharma, MorphoSys AG, Pharmacyclics/Janssen, and SeaGen. He also receives research funding from 4D, Abbvie, Acerta, Adaptimmune, Allogene, Amgen, Bayer, Celgene, Cellectis, EMD, Gilead, Genentech/Roche, Guardant, Iovance, Janssen Pharmaceutical, Kite, MorphoSys, Nektar, Novartis, Pfizer, Pharmacyclics, Sanofi, Takeda, TGTherapeutics, Xencor, Ziopharm, the Burroughs Wellcome Fund, the Eastern Cooperative Oncology Group, the National Cancer Institute (NCI), NIH, the V Foundation, and the Cancer Prevention and Research Institute of Texas: CPRIT Scholar in Cancer Research. RA receives research funding from Merck, holds patents on PD-1–directed immunotherapy, and is listed as a co-inventor on an Emory University–held patent for SARS-CoV-2 serology assays (patent nos. PCT/US2021/030461 and 11359013).

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Research Funding:

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
  • Life Sciences & Biomedicine
  • Medicine, Research & Experimental
  • Research & Experimental Medicine
  • T-CELL RESPONSES
  • RICHTER TRANSFORMATION
  • INFECTION
  • MEMORY
  • PROLIFERATION
  • INTERFERON
  • SERIES
  • BLOOD
  • ASSAY

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

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Journal Title:

JOURNAL OF CLINICAL INVESTIGATION

Volume:

Volume 132, Number 18

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Article | Final Publisher PDF

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.

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© 2022 Chang et al.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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