High expression of OX-40, ICOS, and low expression PD-L1 of follicular helper and follicular cytotoxic T cells in chronic lymphocytic leukemia

Gelmez M. Y., Oktelik F. B., Çınar S., Ozbalak M., Ozluk O., Aktan M., ...More

JOURNAL OF HEMATOPATHOLOGY, vol.15, no.3, pp.117-129, 2022 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 15 Issue: 3
  • Publication Date: 2022
  • Doi Number: 10.1007/s12308-022-00497-5
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, EMBASE
  • Page Numbers: pp.117-129
  • Keywords: ICOS, PD-L1, OX-40, T follicular cell, CLL, Chronic lymphocytic leukemia, MOLECULAR-MECHANISMS, B-CELLS, AID, OX40, ASSOCIATION, CYTOKINE, LYMPHOMA, LIGAND, TUMOR
  • Istanbul University Affiliated: Yes


Chronic lymphocytic leukemia (CLL) is the most common leukemia in the elderly. T follicular helper (T-FH) and follicular cytotoxic T (T-FC) cells are a subset of CD4(+) and CD8(+) T cells expressing CXCR5, respectively. OX-40, ICOS, and PD-L1 are secondary immune checkpoint molecules and have a role in the maintenance of an immune response. The literature about the role of ICOS, OX-40, and PD-L1 receptors of T-FH and, especially T-FC cells, in CLL is limited. In this study, peripheral blood mononuclear cells (PBMCs) were isolated from heparinized blood samples by density gradient centrifugation using Ficoll-Paque from 34 CLL patients and 19 healthy subjects. The expression of ICOS, OX-40, and PD-L1 of T-FC and T-FH cells in CLL patients was investigated by flow cytometry. According to healthy subjects, T-FH and T-FC cell levels were increased in CLL patients. High-ICOS and low-PD-L1 expression in T-FH cells and high OX-40 and ICOS, low-PD-L1 expression in TFC cells of CLL patients compared to healthy subjects. OX-40 expression was positively correlated with T-FH and T-FC cells levels [R = 0.504, (p = 0.002) and R = 0.316, (p = 0.05)]. Additionally, OX-40 expression of T-FH was positively correlated with ICOS expression [R = 0.660, (p < 0.001)] and PD-L1 expression [R = 0.649, (p < 0.001)]. OX-40L, ICOS, and PD-L1 expression of B cells were elevated in CLL patients compared to healthy subjects. OX-40L expression of B cells was positively correlated with ICOSL expression [R = 0.568, (p = 0.0004)] and PD-L1 expression. Elevated CD4(+) CXCR5(+) T-FH and CD8(+)CXCR5(+) T-FC cells with high OX-40 and ICOS activator and low-PD-1L inhibitor receptor expression in CLL patients might have a role in the pathogenesis of CLL.