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Jeremy S. Abramson, MD, MMSc
Jeremy S. Abramson, MD, MMSc
Posted: Tuesday, May 31, 2022
Hui Yang, PhD, of Nanjing Medical University, China, and colleagues proposed that BCL2 expression in the T cells of patients with chronic lymphocytic leukemia (CLL) appears to be associated with immunosuppression, from the promotion of regulatory T-cell abundance and cytotoxic T lymphocytes. Additionally, the study authors suggested a positive correlation between BCL2 expression in T cells and serum β2-microglobulin levels. The study findings were published in Molecular Cancer.
“We demonstrated that the BCL2-positive T cells of patients with chronic lymphocytic leukemia exhibit profound defects in T-cell functions and T-cell differentiation,” said the authors.
The study enrolled 266 patients with CLL from Jiangsu Province Hospital from January 2017 to December 2021. Blood samples were taken from all patients.
The study found a significant increase in BCL2 expression in the T cells of all patients enrolled. Single-cell RNA sequencing indicated that BCL2+CD4+ T cells had the gene signature of increased regulatory T cells. Single-cell RNA sequencing of BCL2+CD8+ T cells showed the gene signature of exhausted cytotoxic T lymphocytes. Additionally, this shows the increased expression of BCL2 was associated with T-cell activation and cellular adhesion.
The results from single-cell RNA sequencing were verified in peripheral T cells from 70 patients with CLL, wherein BCL2+CD4+ T cells were enriched with regulatory T cells and had higher expression of interleukin 10 and transforming growth factor-β than BCL2-CD4+ T cells. BCL2 expression in CD8+ T cells was associated with exhausted cells (PD-1+Tim-3+) and weak expression of granzyme B and perforin. The T cell–associated cytokine profiling revealed a negative association between BCL2+ T cells and T-cell activation. Patients with CLL in complete remission after treatment with venetoclax were observed to have decreased frequencies and recovery functions of BCL2+ T cells.
Disclosure: The study authors reported no conflicts of interest.
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