Clinicopathological features of programmed cell death-1 and programmed cell death-ligand-1 expression in the tumor cells and tumor microenvironment of angioimmunoblastic T cell lymphoma and peripheral T cell lymphoma not otherwise specified

Abstract

The expression patterns of programmed cell death-1 (PD-1) and programmed cell death-ligand-1 (PD-L1) and their clinicopathological implications were investigated in peripheral T cell lymphoma (PTCL) including angioimmunoblastic T cell lymphoma (AITL) and PTCL-not otherwise specified (PTCL-NOS). PTCL-NOS was further classified into nodal PTCL with follicular helper T cell (Tfh) phenotype ("PTCL-Tfh_new") and "PTCL-NOS_new". PD-1 and PD-L1 expression on tumor cells and reactive immune cells was evaluated using immunohistochemistry. PD-1 and PD-L1 expression on tumor cells (PD-1^T and PD-L1^T, respectively) was interpreted as positive when more than 5% of tumor cells expressed PD-1 or PD-L1. For PD-1 and PD-L1 on tumor cells and/or reactive immune cells (PD-1^{T + IC} and PD-L1^{T + IC}, respectively), a cutoff of 10% of cells was used. PD-1^T, PD-L1^T, and PD-L1^{T + IC} expressions tended to be higher in AITLs than in PTCLs-NOS. PD-1^T, PD-1^{T + IC}, PD-L1^T, and PD-L1^{T + IC} expressions tended to be higher in PTCLs with Tfh phenotype including AITLs and "PTCL-Tfh_new" than in PTCLs without Tfh phenotype. The serum LDH level was significantly elevated in patients with PTCL positive for PD-L1^T (P = 0.006) and PD-L1^{T + IC} (P < 0.001). Patients with PTCL who were positive for combined expression of PD-1^T/PD-L1^{T + IC} presented at older ages (P = 0.010), nodal diseases (P = 0.001), higher IPI (P = 0.060), and elevated LDH (P = 0.030). Combined PD-1^T/PD-L1^{T + IC} positivity was related to shorter overall survival in patients with AITL (P = 0.051). Combined PD-1^T/PD-L1^{T + IC} positivity was a significant poor prognostic factor in patients with stage IV AITL, independent of B symptoms and performance status (HR = 6.282 [CI, 1.655-23.844], P = 0.007). In summary, the PD-1/PD-L1 pathway could be a potential prognostic and therapeutic biomarker for PTCL.

Keywords: Angioimmunoblastic T cell lymphoma; Cancer immunotherapy; Immune checkpoint; Peripheral T cell lymphoma; Programmed cell death-1; Programmed cell death-ligand-1.