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γδ T Are Significantly Impacted by CLL Burden but Only Mildly Influenced by M-MDSCs

Michał Zarobkiewicz1, Wioleta Kowalska1, Agata Szymańska1

  • 1Department of Clinical Immunology, Medical University of Lublin, 20-093 Lublin, Poland.

Cancers
|January 25, 2025
PubMed

Insights

This study found that myeloid-derived suppressor cells (M-MDSCs) have a minimal effect on gamma delta T cells in chronic lymphocytic leukemia (CLL). Other factors likely cause the immunosuppression observed in CLL patients.

Area of Science:

  • Immunology
  • Oncology
  • Cellular Biology

Background:

  • Chronic lymphocytic leukemia (CLL) is associated with impaired immune function.
  • Gamma delta (γδ) T cells play a role in anti-tumor immunity.
  • The role of myeloid-derived suppressor cells (M-MDSCs) in CLL-induced immunosuppression requires further elucidation.

Purpose of the Study:

  • To investigate the impact of CLL on γδ T cells.
  • To assess the in vitro effect of M-MDSCs on γδ T cells to understand immunosuppression sources.

Main Methods:

  • Flow cytometry analysis of γδ T cells (including NKG2D, Fas, FasL, TRAIL) in 163 CLL patients and 34 healthy controls.
  • In vitro co-culture experiments with γδ T cells and M-MDSCs.
  • RNA sequencing (RNAseq) to analyze transcriptomic changes.

Main Results:

  • RNAseq showed minor transcriptomic alterations in γδ T cells.
  • Cytotoxic potential of γδ T cells against CLL cells was slightly reduced.
  • Depletion of M-MDSCs did not restore the proliferative capacity of γδ T cells.

Conclusions:

  • M-MDSCs appear to have a limited impact on activated γδ T cells in the context of CLL.
  • Mechanisms other than M-MDSCs are likely responsible for the negative effects of CLL on circulating γδ T cells.
Abstract

Keywords:
M-MDSCchronic lymphocytic leukaemia (CLL)gamma delta Timmunosuppressionγδ T

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