TY - JOUR
T1 - PD-L1 expression on tumor or stromal cells of nodal cytotoxic T-cell lymphoma
T2 - A clinicopathological study of 50 cases
AU - Yamashita, Daisuke
AU - Shimada, Kazuyuki
AU - Kohno, Kei
AU - Kogure, Yasunori
AU - Kataoka, Keisuke
AU - Takahara, Taishi
AU - Suzuki, Yuka
AU - Satou, Akira
AU - Sakakibara, Ayako
AU - Nakamura, Shigeo
AU - Asano, Naoko
AU - Kato, Seiichi
N1 - Funding Information:
The authors would like to thank Y. Katayama, Y. Inagaki, K. Matsubara and K. Kito for technical assistance; and the following collaborators for providing patient clinical data and specimens: Aichi Cancer Center Hospital, Aichi Medical University Hospital, Handa City Hospital, Hyogo Cancer Center, Ichinomiya Municipal Hospital, Kanazawa Medical University Hospital, Japanese Red Cross Kyoto Daiichi Hospital, Kariya Toyota General Hospital, Konan Kosei Hospital, Nagoya Ekisaikai Hospital, Oita Prefectural Hospital, Okayama University Hospital, Ogaki Municipal Hospital, Seirei Hamamatsu General Hospital and University Hospital Kyoto Prefectural University School of Medicine. This work was partly supported by Grants-in-Aid for Young Scientists (B) from the Ministry of Education, Culture, Sports, Science, and Technology, Japan (Grant Number JP15K19052).
Funding Information:
The authors would like to thank Y. Katayama, Y. Inagaki, K. Matsubara and K. Kito for technical assistance; and the following collaborators for providing patient clinical data and specimens: Aichi Cancer Center Hospital, Aichi Medical University Hospital, Handa City Hospital, Hyogo Cancer Center, Ichinomiya Municipal Hospital, Kanazawa Medical University Hospital, Japanese Red Cross Kyoto Daiichi Hospital, Kariya Toyota General Hospital, Konan Kosei Hospital, Nagoya Ekisaikai Hospital, Oita Prefectural Hospital, Okayama University Hospital, Ogaki Municipal Hospital, Seirei Hamamatsu General Hospital and University Hospital Kyoto Prefectural University School of Medicine. This work was partly supported by Grants‐in‐Aid for Young Scientists (B) from the Ministry of Education, Culture, Sports, Science, and Technology, Japan (Grant Number JP15K19052).
Publisher Copyright:
© 2020 The Authors. Pathology International published by Japanese Society of Pathology and John Wiley & Sons Australia, Ltd
PY - 2020/8/1
Y1 - 2020/8/1
N2 - 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.
AB - 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.
KW - Epstein–Barr virus
KW - TCR phenotype
KW - cytotoxic molecule
KW - neoplastic PD-L1 expression
KW - peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS)
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U2 - 10.1111/pin.12950
DO - 10.1111/pin.12950
M3 - Article
C2 - 32424876
AN - SCOPUS:85084848681
SN - 1320-5463
VL - 70
SP - 513
EP - 522
JO - Acta Pathologica Japonica
JF - Acta Pathologica Japonica
IS - 8
ER -
