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 TCRαβ type, three were TCRγδ 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 TCRγδ‐type nodal CTL cases showed nPD‐L1 or miPD‐L1 positivity (3 and 10 cases, respectively). TCRγδ‐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 TCRγδ type, are potential candidates for anti‐PD‐1/PD‐L1 therapies.