TIGIT expressing CD4+T cells represent a tumor-supportive T cell subset in chronic lymphocytic leukemia

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OncoImmunology. Taylor & Francis. 2017, 7(1), e1371399. ISSN 2162-4011. eISSN 2162-402X. Available under: doi: 10.1080/2162402x.2017.1371399
Zusammenfassung

While research on T cell exhaustion in context of cancer particularly focuses on CD8+ cytotoxic T cells, the role of inhibitory receptors on CD4+ T-helper cells have remained largely unexplored. TIGIT is a recently identified inhibitory receptor on T cells and natural killer (NK) cells. In this study, we examined TIGIT expression on T cell subsets from CLL patients. While we did not observe any differences in TIGIT expression in CD8+ T cells of healthy controls and CLL cells, we found an enrichment of TIGIT+ T cells in the CD4+ T cell compartment in CLL. Intriguingly, CLL patients with an advanced disease stage displayed elevated numbers of CD4+ TIGIT+ T cells compared to low risk patients. Autologous CLL-T cell co-culture assays revealed that depleting CD4+ TIGIT+ expressing T cells from co-cultures significantly decreased CLL viability. Accordingly, a supportive effect of TIGIT+CD4+ T cells on CLL cells in vitro could be recapitulated by blocking the interaction of TIGIT with its ligands using TIGIT-Fc molecules, which also impeded the T cell specific production of CLL-prosurvival cytokines. Our data reveal that TIGIT+CD4+T cells provide a supportive microenvironment for CLL cells, representing a potential therapeutic target for CLL treatment.

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570 Biowissenschaften, Biologie
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chronic lymphocytic leukemia, T cell exhaustion, TIGIT, PD-1, microenvironment
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ISO 690CATAKOVIC, Kemal, Franz Josef GASSNER, Christoph RATSWOHL, Nadja ZABORSKY, Stefan REBHANDL, Maria SCHUBERT, Markus STEINER, Julia C. GUTJAHR, Lisa PLEYER, Roland GEISBERGER, 2017. TIGIT expressing CD4+T cells represent a tumor-supportive T cell subset in chronic lymphocytic leukemia. In: OncoImmunology. Taylor & Francis. 2017, 7(1), e1371399. ISSN 2162-4011. eISSN 2162-402X. Available under: doi: 10.1080/2162402x.2017.1371399
BibTex
@article{Catakovic2017-09-21TIGIT-69212,
  year={2017},
  doi={10.1080/2162402x.2017.1371399},
  title={TIGIT expressing CD4+T cells represent a tumor-supportive T cell subset in chronic lymphocytic leukemia},
  number={1},
  volume={7},
  issn={2162-4011},
  journal={OncoImmunology},
  author={Catakovic, Kemal and Gassner, Franz Josef and Ratswohl, Christoph and Zaborsky, Nadja and Rebhandl, Stefan and Schubert, Maria and Steiner, Markus and Gutjahr, Julia C. and Pleyer, Lisa and Geisberger, Roland},
  note={Article Number: e1371399}
}
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