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CD2 costimulation strength: A key regulator of T cell function and anti-tumor immunity that is epigenetically

Philippos Demetriou1, Maria Iakovou1, Gregoria Gregoriou1

  • 1The Center for the Study of Haematological and Other Malignancies, Nicosia, Cyprus.

Iscience
|December 11, 2025
PubMed

Insights

Tumor-infiltrating T cells show reduced CD2 expression. The study identifies BAP1 (BRCA1-associated protein 1) as crucial for maintaining CD2 and other T cell receptor levels, impacting T cell function.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cancer Research

Background:

  • CD2 is a critical costimulatory receptor on human T cells.
  • Regulation of CD2 surface abundance and its functional role are not fully understood.
  • CD2 expression is notably decreased on T cells within human brain tumors.

Purpose of the Study:

  • To identify factors that regulate CD2 expression on T cells.
  • To investigate the functional consequences of altered CD2 expression in the tumor microenvironment.

Main Methods:

  • Genome-wide CRISPR-Cas9 screening in Jurkat T cells.
  • Transcriptomic analysis to assess gene expression changes.
  • Functional assays measuring T cell proliferation and cytokine production (IFN-γ).

Main Results:

  • BAP1 (BRCA1-associated protein 1) and SUZ12 were identified as key regulators of CD2 expression.
  • Loss of BAP1 led to downregulation of CD2, TRAC, and other costimulatory receptors, even after T cell activation.
  • BAP1 deficiency disrupted T cell identity and differentiation programs; histone deacetylase inhibition partially restored CD2 expression.
  • Reduced CD2 costimulation in primary human T cells impaired proliferation and IFN-γ production.

Conclusions:

  • BAP1 is a central regulator of costimulatory receptor expression, including CD2.
  • CD2 plays a tunable role in modulating human T cell responses, particularly in the context of tumors.
  • Understanding BAP1-mediated regulation of CD2 could offer therapeutic strategies for enhancing anti-tumor immunity.
Keywords:
immunologymicroenvironment

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