Prognostic value of the co-stimulatory molecule OX40 expression in Extranodal Natural Killer/T-cell Lymphoma

To explore the clinicopathological features and the prognostic values of the co-stimulatory molecules OX40 and the inducible T-cell co-stimulator (ICOS) in Extranodal Natural Killer/T-cell Lymphoma (ENKTL).

82 participants (median age 51 years, 26.8% female) were included in this study. OX40 and ICOS expression was detected using immunohistochemistry on paraffin‑embedded sections. The level of OX40 and ICOS expression was categorized into negative (0%, no staining) and positive groups. Kaplan-Meier analysis was used to estimate the probability of survival rates, and group comparisons were made using the Log-rank test.

Positive staining for OX40 and ICOS was observed in 64 (78.0%) and 48 (58.5%) cases, respectively. The main differences between OX40-positive and OX40-negative were in the Chinese Southwest Oncology Group and Asia Lymphoma Study Group ENKTL (CA) stage, Korean Prognostic Index (KPI), CD68, PD1, PDL1, and CD152. Patients exhibiting positive OX40 expression demonstrated a statistically significant improvement in survival compared to the negative group (p < 0.001). However, no statistically significant survival difference was observed between ICOS-negative and ICOS-positive patients (p = 0.760). The expression of OX40 was a favorable prognostic indicator for ENKTL patients (Hazard Ratio = 0.049, 95% confidence interval: 0.009-0.285, p < 0.001) in multivariable analysis.

Our findings reveal that positive OX40 expression serves as an independent prognostic marker for improved survival of ENKTL, suggesting its potential utility in stratifying patient risk and optimizing treatment strategies. Future research should focus on the therapeutic targeting of OX40 in ENKTL.