PD-L1 and PD1 expression in post-transplantation lymphoproliferative disease (PTLD) of childhood and adolescence: An inter- and intra-individual descriptive study covering the whole spectrum of PTLD categories.

Therapy of children with post-transplantation lymphoproliferative disorder (PTLD) after hematopoietic stem cell (HSCT) and solid organ transplantation (SOT) can be challenging. In this retrospective study, we investigated PD-L1 and PD1 expression in all PTLD categories of childhood and adolescence to see whether checkpoint inhibition with PD-L1/PD1 inhibitors may serve as a therapy option. We included 21 patients aged 19 years or younger (at date of transplant) with PTLD following SOT or HSCT having adequate tumor samples available (n = 29). Using immunohistochemistry, we evaluated PD-L1/PD1 expression on both tumor cells and cells of the microenvironment in all samples. Availability of consecutively matched tumor samples during 6 of 21 patients' disease courses also allowed an intra-individual assessment of PD-L1/PD1 expression. We observed lower PD-L1 and higher PD1 expression in non-destructive lesions, and higher PD-L1 and lower PD1 expression in polymorphic and, in particular, in monomorphic PTLD, mostly diffuse large B-cell lymphomas (DLBCL, n = 10/21). The amount of PD-L1- and PD1-positive cells changed in the opposite way in sequential biopsies of the same individual correlating well with the PTLD category. This is the first comprehensive pediatric study assessing PD-L1 and PD1 expression on tumor cells and in the microenvironment of PTLD including not only monomorphic, but also non-destructive early lesions. PD-L1 expression of the tumor cells inversely correlated with PD1 expression in surrounding tissues, with the highest expression in DLBCL. Since PTLD can be therapeutically challenging, our results indicate a potential efficacy of checkpoint inhibitors if standard immune- and/or chemotherapy fail or are impossible. We therefore recommend routine staining of PD-L1 and PD1 in all PTLD categories.