Expression and prognostic value of cytotoxic T-lymphocyte-associated 4 protein in classic Hodgkin lymphoma


Sahin T. K., Gungor H. N., Gezmis E., Sahin E. A., BARIŞTA İ., AYHAN E. A., ...More

Expert Review of Hematology, 2026 (SCI-Expanded, Scopus)

  • Publication Type: Article / Article
  • Publication Date: 2026
  • Doi Number: 10.1080/17474086.2026.2680139
  • Journal Name: Expert Review of Hematology
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Chemical Abstracts Core, EMBASE, MEDLINE, Health Research Premium Collection (ProQuest), Pharma Collection (ProQuest)
  • Keywords: CTLA-4 expression, Hodgkin lymphoma, prognosis, survival, tumor microenvironment
  • Hacettepe University Affiliated: Yes

Abstract

Background: Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is a key inhibitory immune checkpoint expressed predominantly on activated and regulatory T cells. Although immune evasion mechanisms are central to the pathobiology of classic Hodgkin lymphoma (cHL), the prognostic significance of CTLA-4 expression remains insufficiently defined. This study aimed to evaluate the association between CTLA-4 expression, clinicopathologic characteristics, and survival outcomes in patients with cHL who received ABVD as first-line therapy. Research design and methods: This retrospective single-center study included 77 adult patients with cHL treated with ABVD as first-line therapy. CTLA-4 expression was assessed by immunohistochemistry in diagnostic biopsy specimens and categorized as negative (<10%), low (10–50%), or high (>50%). Results: High CTLA-4 expression was significantly associated with younger age, female sex, mixed cellularity histology, and advanced-stage disease (all p < 0.05). High CTLA-4 expression was associated with significantly inferior recurrence-free survival (RFS) and overall survival (OS) compared with lower expression levels. Conclusions: CTLA-4 expression represents a clinically relevant biomarker associated with adverse disease characteristics and poorer survival in cHL. Routine assessment of CTLA-4 may enhance risk stratification and help identify patients who could benefit from intensified monitoring or novel immunotherapeutic strategies.