PD-L1 expression on tumor or stromal cells of nodal cytotoxic T-cell lymphoma: A clinicopathological study of 50 cases.

Inhibitors of programmed cell-death 1 (PD-1) and programmed cell-death ligand 1 (PD-L1) have revolutionized cancer therapy. Nodal cytotoxic T-cell lymphoma (CTL) is characterized by a poorer prognosis compared to nodal non-CTLs. Here we investigated PD-L1 expression in 50 nodal CTL patients, with and without EBV association (25 of each). We identified seven patients (14%) with neoplastic PD-L1 (nPD-L1) expression on tumor cells, including three males and four females, with a median age of 66 years. One of the seven cases was TCR alpha beta type, three were TCR gamma delta type and three were TCR-silent type. Six of the seven cases exhibited a lethal clinical course despite multi-agent chemotherapy, of whom four patients died within one year of diagnosis. Morphological findings were uniform, with six cases showing centroblastoid appearance. Among nPD-L1(+) cases, two of three examined had structural variations of PD-L1 disrupting 3 '-UTR region. Notably, all of the TCR gamma delta-type nodal CTL cases showed nPD-L1 or miPD-L1 positivity (3 and 10 cases, respectively). TCR gamma delta-type cases comprised 42% of nPD-L1(+) cases (P = 0.043 vs. PD-L1(-)), and 35% of miPD-L1(+) cases (P = 0.037 vs. PD-L1(-)). The results indicate that PD-L1(+) nodal CTL cases, especially of the TCR gamma delta type, are potential candidates for anti-PD-1/PD-L1 therapies.