Introduction: PD-L1 expression on select tumor cells engages the PD-1 receptor on T cells, inhibiting anti-tumor immune responses. PD-L1 has been detected in cases of post-transplant lymphoproliferative disorder (PTLD), though data is limited and clinical correlation is lacking. In this study, we examine PD-L1 expression in PTLD and evaluate for clinical correlation. Methods: We identified 21 PTLD cases in kidney transplant recipients diagnosed at our institution from 2/1996 to 4/2017. Using paraffin-embedded tissue biopsies, we examined 21 primary tumors for expression of PD-L1 using PD-L1 monoclonal antibody performed with PAX5 as a double stain. We scored expression of PDL-1 on lesional B-cells (identified with PAX5) as a percentage of positive cells. Clinical course and outcome were obtained from retrospective chart review. Results: Patient ages at diagnosis ranged from 2.4 to 20.8 years with median follow up time of 3.5 years (range 0.1-13.6). 2 patients transferred care shortly after diagnosis. Of those treated at our institution, 5 received chemotherapy and 3 died from PTLD. One fatality developed graft failure during therapy. Applying revised 2017 WHO classification showed 6 non-destructive PTLDs (4 infectious mononucleosis and 2 florid follicular hyperplasia), 9 Polymorphic PTLD cases and 8 monomorphic PTLD cases (6 diffuse large B-cell lymphomas and 2 Burkitt lymphomas). The median number of B-cells expressing PDL1 in all cases is 30% (range 5-90). The average PD-L1 expression by subtypes of PTLD is as follows: Non-destructive PTLD 11%, polymorphic PTLD 43% and monomorphic PTLD 73% (p=0.01). EBV positive PTLD cases (17/21, 81%) also showed higher PD-L1 expression (49% vs 21%, p=0.023) as compared with EBV negative PTLD cases.

Conclusion: Significant differences in PD-L1 expression are seen among different subtypes of PTLDs with monomorphic PTLDs showing highest expression. Among 3 patients who died of their disease, 90% of lesional B-cells expressed PD-L1. This study suggests use of PD-L1 directed therapies should be considered in select cases of monomorphic PTLDs, particularly in those whose transplant is not life-sustaining.

CITATION INFORMATION: Rodig N., Pinkus G., Ramos Gonzalez G., Agur T., Weinberg O. Programmed Cell Death Ligand 1 (PD-L1) Expression is Associated with Subtypes of Post-Transplant Lymphoproliferative Disorders (PTLD) Am J Transplant. 2017;17 (suppl 3).

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