PD-L1 and PD-1 expression in pediatric post-transplant Burkitt lymphoma and other monomorphic post-transplant lymphoproliferative disorders

Background: Post-transplant lymphoproliferative disorders (PTLD) develop as a consequence of immune suppression. Programmed death protein 1 (PD-1), a regulator of host immune activation, binds to programmed death-ligand 1 (PD-L1) to suppress the T-cell immune response. PD-1/PD-L1 pathway may play a role in PTLD. The objective was to describe intratumoral expression of PD-L1 and PD-1 in pediatric monomorphic PTLD, and assess if density of these cells is associated with progression-free survival (PFS) and overall survival (OS).

Procedure: Clinical variables and outcome data were collected on B-cell monomorphic PTLD treated in Toronto, Canada between 2000 and 2017. Diagnostic area from tumor tissue was identified to count CD3-positive or PD-1-positive cells and CD3-negative lymphoma B cells or PD-L1-positive cells. CD3⁺ , PD-1⁺ , and PD-L1⁺ cell densities were compared between cases of PTLD. OS and PFS were analyzed.

Results: We identified 25 cases of B-cell monomorphic PTLD; majority Burkitt lymphoma (32%) and diffuse large B-cell lymphoma (56%). All cases had CD3⁺ cells infiltrating the tumor, and median percentage of CD3⁺ cells was 14% (interquartile range: 6.2%-25%). Twelve cases (48%) had PD-1⁺ cell infiltrating (range: 1%-83%) and 13 cases (52%) had no PD-1⁺ cells infiltrating. Sixteen cases (64%) had PD-L1⁺ cells present; however, there was no PD-L1 expression on any Burkitt lymphoma tissue. When comparing PD-1 and PD-L1 expression, there was no difference in OS or PFS.

Conclusion: Intratumoral presence of PD-1⁺ and PD-L1⁺ cells varied in pediatric patients with monomorphic PTLD; however, no relationship to OS and PFS was identified.