Background
Classical Hodgkin's lymphoma (cHL) in adolescents between 15 and 18 years old shows a higher disease-related mortality, and the overall prognosis is worse than in both children and adults. Objectives: We investigated the immune checkpoint inhibitors (ICPIs) therapeutic targets and specific T-regulatory and cytotoxic T-cell subsets in the subgroup of adolescent cHL patients, and we challenged their prognostic power.
Conclusions
We showed that microenvironment of cHL in adolescent patients is enriched with potential therapeutic targets of ICPI that may be considered for therapeutic applications. Furthermore, the presence of PD-1 expressing T-cells strongly relates to advanced stage disease and a low density of CD8+ T lymphocytes is associated with recurrence and progression of disease.
Methods
We retrieved formalin-fixed paraffin-embedded (FFPE) tissue of adolescent patients diagnosed with cHL and tested by immunohistochemistry the immune checkpoint molecules CTLA-4, LAG-3, PD-1, and PDL1 as well as the biological markers FOXP3 and CD8.
Results
All the cases of our cohort expressed the immune checkpoint molecules CTLA-4, LAG-3, and PD-1 in microenvironment (ME), and the number of PD1+ cells was strongly associated with advanced disease, being higher in stage III/IV, indicating a possible role in the progression of cHL. A higher risk of recurrence and progression occurred in patients with lower amount of CD8+ microenvironmental T-cells at diagnosis (67.14 ± 27.23 vs. 42.86 ± 17.33 p = 0.032 and 65.59 ± 26.68 vs. 37 ± 17.45 p = 0.046, respectively). Conclusions: We showed that microenvironment of cHL in adolescent patients is enriched with potential therapeutic targets of ICPI that may be considered for therapeutic applications. Furthermore, the presence of PD-1 expressing T-cells strongly relates to advanced stage disease and a low density of CD8+ T lymphocytes is associated with recurrence and progression of disease.