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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. 1 Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
  2. 2 Department 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}


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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  • 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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