The perivascular microenvironment in Epstein-Barr virus positive primary central nervous system lymphoma: The role of programmed cell death 1 and programmed cell death ligand 1.

It has been shown that high expression of certain immune checkpoint molecules, including those of the programmed death protein 1/programmed death ligand 1 (PD-1/PD-L1) axis, can be utilized to regulate immunosuppression in the microenvironment of malignant neoplasms. For the purpose of clarifying the immune-escape mechanism of primary central nervous system lymphomas (PCNSLs), particularly in Epstein-Barr virus (EBV)-positive cases, markers for PD-1, PD-L1, tumor-associated macrophages (TAMs), and tumor-infiltrating lymphocytes (TILs) in 39 surgical specimens of PCNSLs (17 EBV-positive, 22 EBV-negative) were investigated by immunohistochemistry. Staining for PD-L1 was scored as follows: (-), no staining; (1+), 0-30% positive cells; (2+), 30-60% positive cells; and (3+), >60% positive cells. In EBV-positive cases, PD-L1 was detected in both lymphoma cells and TAMs in 12/17 cases, and in TAMs only in 4/17 cases. The mean number of PD-1, TIA-1 (a marker for cytotoxic T-cells), and FOXP3 (a marker for regulatory T-cells)-positive TILs in EBV-positive cases was 36.4 ± 45.9, 390 ± 603, and 9.88 ± 15.1, respectively. In EBV-negative cases, PD-L1 was detected in both lymphoma cells and TAMs in 11/22 cases, and in TAMs only in 4/22 cases. The mean of PD-1, TIA-1 and FOXP3-positive lymphocytes in EBV-negative cases was 67.3 ± 82.0, 158 ± 206 and 9.32 ± 17.5, respectively. We found no significant difference in the number of FOXP3-positive, lymphocytes between EBV-positive and negative cases. However, there were significantly higher numbers of PD-1-positive lymphocytes in the former, and significantly higher numbers of TIA-1-positive lymphocytes in the latter (P < 0.05). The combined data indicate that expression of PD-L1 by lymphoma cells and TAMs mediate the trafficking of TILs, which may explain the immune-escape process of PCNSLs. In addition, EBV infection appears to affect the trafficking mechanism of TILs, and may thus play an important role in the microenvironment immunity of these tumors.

Sugita Y ，Furuta T ，Ohshima K ，Komaki S ，Miyoshi J ，Morioka M ，Abe H ，Nozawa T ，Fujii Y ，Takahashi H ，Kakita A ... -  《-》

Clinicopathological evaluation of the programmed cell death 1 (PD1)/programmed cell death-ligand 1 (PD-L1) axis in post-transplant lymphoproliferative disorders: association with Epstein-Barr virus, PD-L1 copy number alterations, and outcome.

The clinical implications of the programmed cell death 1 (PD1)/programmed cell death-ligand 1 (PD-L1) axis in patients with post-transplant lymphoproliferative disorders are largely unknown, and its association with Epstein-Barr virus (EBV) status and PD-L1 copy number alterations (CNAs) has not been thoroughly studied. PD1/PD-L1 expression was studied in 50 adult post-transplant lymphoproliferative disorders, and the correlations with PD-L1 CNAs, EBV, clinicopathological features and outcome were evaluated. Thirty-seven (74%) cases were classified as diffuse large B-cell lymphoma (DLBCL), nine (18%) cases were classified as polymorphic, and four (8%) cases were classified as classic Hodgkin lymphoma. Thirty-four cases were EBV-positive, with 29 of 34 (85%) having latency II or III, and 15 of 34 (44%) having viral replication. PD-L1 expression in tumour cells and tumour-associated macrophages was observed in 30 (60%) and 37 (74%) cases, respectively. PD1 positivity was seen in 16 (32%) cases. PD-L1 expression was associated with EBV with latency II or III (P = 0.001) and organ rejection (P = 0.04), and, in DLBCL, with non-germinal centre type DLBCL (P < 0.001). Cases with PD-L1-positive tumour cells showed a higher number of PD-L1 CNAs than PD-L1-negative cases (P = 0.001). Patients with EBV/latency III/replication and simultaneous PD-L1 expression showed the worst overall survival (P < 0.001). The PD1/PD-L1 axis is deregulated in post-transplant lymphoproliferative disorders, with frequent PD-L1 expression and PD1 negativity. PD-L1 expression is associated with EBV latency II or III and PD-L1 CNAs, and probably reflects a proinflammatory tumour microenvironment. The combined analysis of EBV status and PD-L1 expression may help to identify deeply immunosuppressed patients who can benefit from immune reconstitution approaches.

Veloza L ，Teixido C ，Castrejon N ，Climent F ，Carrió A ，Marginet M ，Soldini D ，González-Farré B ，Ribera-Cortada I ，Lopez-Guillermo A ，González-Barca E ，Sierra A ，Herrera M ，Gómez C ，Garcia A ，Balagué O ，Campo E ，Martinez A ... -  《-》

Poor prognosis in Epstein-Barr virus-negative gastric cancer with lymphoid stroma is associated with immune phenotype.

Cho CJ ，Kang HJ ，Ryu YM ，Park YS ，Jeong HJ ，Park YM ，Lim H ，Lee JH ，Song HJ ，Jung HY ，Kim SY ，Myung SJ ... -  《-》

Characterization of PD-L1 and PD-1 Expression and CD8+ Tumor-infiltrating Lymphocyte in Epstein-Barr Virus-associated Nasopharyngeal Carcinoma.

Larbcharoensub N ，Mahaprom K ，Jiarpinitnun C ，Trachu N ，Tubthong N ，Pattaranutaporn P ，Sirachainan E ，Ngamphaiboon N ... -  《-》

Characterisation of tumour microenvironment and immune checkpoints in primary central nervous system diffuse large B cell lymphomas.

Alame M ，Pirel M ，Costes-Martineau V ，Bauchet L ，Fabbro M ，Tourneret A ，De Oliveira L ，Durand L ，Roger P ，Gonzalez S ，Cacheux V ，Rigau V ，Szablewski V ... -  《-》