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Expression of the checkpoint receptors LAG-3, TIM-3 and VISTA in peripheral T cell lymphomas
  1. Carlos A Murga-Zamalloa1,
  2. Noah A. Brown2,
  3. Ryan A. Wilcox1
  1. 1Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
  2. 2Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA
  1. Correspondence to Dr Carlos A Murga-Zamalloa, Internal Medicine, University of Michigan, Ann Arbor, MI 48104, USA; carlosmu{at}med.umich.edu

Abstract

Aims Peripheral T cell lymphomas represent approximately 10%–15% of non-Hodgkin lymphomas and are characterised by an aggressive clinical courses and poor outcomes. Ligands provided by constituents of the tumour microenvironment engage receptors expressed by malignant T cells, promoting tumour growth and chemotherapy resistance. In addition to stimulatory receptors that promote the growth and survival of malignant T cells, recent studies suggest that homologous inhibitory receptors may have an opposing effect and function as tumour suppressors. For example, recent data suggest that programmed cell death 1 blockade may lead to increased lymphoma growth. Therefore, the identification of alternative checkpoint receptors in T cell lymphoproliferative neoplasms is an important and clinically relevant question.

Methods The checkpoint receptors T cell immunoglobulin-3 (TIM-3), V-domain Ig-containing suppressor of T cell activation (VISTA) and lymphocyte-activation gene 3 (LAG-3) play fundamental roles in peripheral tolerance, and their ligands are exploited by many solid tumours to evade host immunity. However, their expression in T cell lymphoproliferative neoplasms has not been evaluated. In this study, we evaluated the expression of TIM-3, VISTA and LAG-3 in a cohort of peripheral T cell lymphomas cases by immunohistochemistry and flow cytometric analysis.

Results Our results demonstrate that TIM-3, VISTA and LAG-3 expression is rarely identified within a large cohort of T cell lymphomas and its tumour microenvironment.

Conclusions Our data suggest that immune-regulatory roles for TIM-3, VISTA and LAG-3 may be predominant in lymphomas subsets different than the ones analysed in the current study. However, a potential role for these checkpoint receptors as tumour suppressors in T cell lymphomas remains to be elucidated.

  • checkpoint blockade
  • t-cell lymphoma
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Footnotes

  • Handling editor Mary Frances McMullin.

  • Contributors All authors conceived the idea, designed the study, analysed results and wrote the manuscript. CMZ, RAW and NAB designed, analyzed and interpreted data and wrote the article.

  • Funding Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under award number K08-CA218460 (CMZ) and R01CA217994 (RAW).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.

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