The Triple Positivity for EBV, PD-1, and PD-L1 Identifies a Very High Risk Classical Hodgkin Lymphoma

The programmed death receptor (PD-1) and ligand (PD-L1) pathway act by suppressing the antitumor response in chronic Hodgkin lymphoma (cHL). In this study, we aimed to investigate the effect of PD-1, PD-L1, and Epstein-Barr virus (EBV) positivity on prognosis at the initial diagnosis of cHL.

Thirty-six patients with cHL were retrospectively analyzed. PD-L1 staining was performed for RS cells and tumor microenvironment in the biopsy materials of cases. The presence of EBV was investigated by EBER (EBV-encoded RNA) method in tumor cell. P < .05 was accepted as significant.

The presence of advanced-stage disease, B symptoms, intermediate or high-risk international prognostic index (IPS), and extranodal involvement were found to be related to both PD-L1 positivity and EBV positivity in RS cells. PD-L1 positivity in RS cells was also associated with EBV positivity. There were 6 (16.7%) triple-positive (EBV⁺, RS-PD-L1⁺, mic-PD-1⁺) patients. All of these patients had advanced-stage disease, B symptoms at the time of diagnosis, and intermediate-high IPS score, and 4 of 6 patients had extranodal involvement. This group also had significantly shortened overall survival compared with others (38.4 months vs. 67.9 months P = .024).

Our data suggest that there is correlation between PD-L1 positivity and EBV positivity in tumor RS cells that are also associated with extranodal involvement, intermediate and high IPS score, presence of B symptoms, and advanced-stage disease. In addition, we identified a group of triple-positive (EBV⁺, RS-PD-L1⁺, mic-PD-1⁺) cHL patients who have a very high-risk disease.