Bite-Sized Pieces from EHA 2021: Two New Findings on T-Cell Lymphoma
Can a molecule that is crucial for the sensitivity of adult T-cell lymphoma or leukemia (ATLL) to NK cell cytotoxicity be identified? And what conclusions were drawn from the testing of an antibody specific for TRBC1 in the investigation of T-lymphoproliferative disorders? These topics were also covered at the EHA 2021 congress, in the electronic poster presentation section.
CD48 as a Potential Biomarker in ATLL
ATLL is a neoplasm of mature T lymphocytes associated with a poor prognosis. It is caused by the human T-cell leukemia virus type 1 (HTLV-1), a retrovirus that infects CD4+ T cells in infants. During the prolonged latency period (ATLL can develop in HTLV-1 infected individuals even after more than 50 years), extensive genetic changes and expression of aberrant genes accumulate in the affected cells. The aim of the presented study was to identify molecules in ATLL cells that play a fundamental role in their escape from NK cell-mediated cytotoxicity.
Screening of candidate genes was performed using CRISPR-Cas9 technology on 2 ATLL cell lines. An anti-CCR4 monoclonal antibody was added to the mixture of effector and target cells, allowing evaluation of genes responsible for direct NK cell cytotoxicity and antibody-dependent cell cytotoxicity (ADCC), mediated by the mentioned antibody. In the 2 examined ATLL cell lines, 20 genes overlapped, including CCR4 and CD48. CD48 plays a role in lymphocyte activation. Further experiments confirmed that knocking out the CD48 gene allowed these modified ATLL cells to escape cytotoxicity mediated by both NK cell lines and human primary NK cells.
Researchers found that in primary ATLL cells, mRNA expression of CD48 decreased with decreasing aggressiveness of clinical subtypes. According to the insights from this study, CD48 in ATLL is a fundamental molecule that determines sensitivity to NK cell-mediated cytotoxicity. The authors noted that the described work improved the understanding of the mechanisms by which ATLL escapes immunity and that it could lay the groundwork for evaluating CD48 as a biomarker for future NK cell-based immunotherapies.
TRBC1-Specific Antibody: A New Aid in Flow Cytometry
T-cell lymphomas are a pathologically and clinically complex group of heterogeneous diseases. At the EHA 2021 congress, a study was presented involving the detection of T-cell clonality by flow cytometry in mature T-cell neoplasms using the constant region 1 beta chain of the T-cell receptor (TRBC1). The purpose was to validate the diagnostic capabilities of the anti-TCR C beta 1 antibody, designed specifically to detect clonal abnormalities in TRBC1, by adding it to the existing diagnostic antibody panel. Identification of such an antibody allows determination of T-cell clonality and differentiation of pathological T lymphocytes from normal ones.
The researchers used 10 peripheral blood samples from healthy individuals to establish the normal biological occurrence of TRBC1 in T lymphocytes (control group) and 30 samples obtained from patients for the investigation of lymphoproliferative disorders in a blinded design, independent of findings from molecular analysis. They also assessed TRBC1 expression in CD4+ and CD8+ T lymphocytes (separately).
It was found that the anti-TCR C beta 1 antibody, when combined with the existing diagnostic panel, has high diagnostic value for assessing T-cell clonality in patients suspected of having T-cell neoplasia. The inclusion of the TRBC1-specific antibody improved the identification of clonal T cells and correlated well with molecular methods. The authors believe it represents an excellent aid for investigating T-lymphoproliferative disorders by flow cytometry.
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Sources:
1. Chiba M., Shimono J., Ishio T. et al. EP852 Whole-genome CRISPR library screens identify CD48 as an essential molecule in adult T-cell leukemia/lymphoma for defining susceptibility to natural killer cell-mediated cytotoxicity. EHA, 2021 Jun 9. Available at: https://library.ehaweb.org/eha/2021/eha2021-virtual-congress/325610/masahiro.chiba.whole-genome.crispr.library.screens.identify.cd48.as.an.html
2. Waldron D., O’Brien D., Smyth L. et al. EP885 Reliable detection of T-cell clonality by flow cytometry in mature T-cell neoplasms using TCR β constant region 1 (TRBC1): a comparison with PCR-based clonality testing. EHA, 2021 Jun 9. Available at: https://library.ehaweb.org/eha/2021/eha2021-virtual-congress/325643/deirdre.waldron.reliable.detection.of.t-cell.clonality.by.flow.cytometry.in.html
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