PD1 (CD279) and PD-L1 (CD274, B7H1) expression in primary central nervous system lymphomas (PCNSL)

Background: Primary central nervous system lymphoma (PCNSL) is a malignant brain tumor with limited treatment options and shows prominent infiltration by tumor infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs). Programmed death 1 (PD1; CD279) and its ligand PD-Li (B7H1, CD274) promote escape of tumor cells from immune surveillance in several tumor types, but no data are available on PCNSL. Agents inhibiting PD1 and PD-Li are showing compelling antitumor activity in current clinical trials in solid and hematological cancers. Methods: We investigated PD1 (clone NAT ab52587) and PD-Li (clone 5H1) expression in large neurosurgical resection specimens of 20 immunocompetent historical PCNSL patients using immunohistochemistry. Results: We found expression of PD1 and/or PD-Li on tumor cells, TILs, or TAMs in a total of 18/20 (90%) of PCNSL cases. In 12/20 (60%) cases, intratumoral PD1-positive TILs were present (low density: 9/20, 45%; moderate density: 2/20, 10%; high density: 1/20, 5%) with additional peritumoral accumulation of PD1-positive lymphocytes in all of 12 cases with evaluable adjacent brain tissue on the tissue section. PD-Li expressing intratumoral TAMs were found in 4/20 (20%) tumors. 111 2/20 (10%) and 4/20(20%) specimens, we observed striking PD-Li or PD1 expression on PCNSL tumor cells, respectively. Median number of CD 8-positive TILs was 517/mm(2) (range 75 2,470) and did not correlate with PD1 or PD-Li expression (p > 0.05, Kruskal-Wallis test). Conclusions: PD1 and PDLi are immunohistochemically detectable in PCNSL and may be involved in creating an immunosuppressive microenvironment. Specific immune checkpoint inhibitors may be considered for experimental therapy approaches in this disease.