Expression of immune checkpoint molecules programmed death protein 1, programmed death-ligand 1 and inducible T-cell co-stimulator in mycosis fungoides and Sezary syndrome: association with disease stage and clinical outcome

被引:12
|
作者
Di Raimondo, Cosimo [1 ]
Rubio-Gonzalez, Belen [1 ]
Palmer, Joycelynne [2 ]
Weisenburger, Dennis D. [3 ]
Zain, Jasmine [4 ]
Wu, Xiwei [5 ,6 ]
Han, Zhen [1 ,6 ]
Rosen, Steven T. [6 ]
Song, Joo Y. [3 ]
Querfeld, Christiane [1 ,3 ,4 ,6 ]
机构
[1] City Hope Natl Med Ctr, Div Dermatol, 1500 E Duarte Rd, Duarte, CA 91010 USA
[2] City Hope Natl Med Ctr, Dept Computat & Quantitat Med, Div Biostat, 1500 E Duarte Rd, Duarte, CA 91010 USA
[3] City Hope Natl Med Ctr, Dept Pathol, 1500 E Duarte Rd, Duarte, CA 91010 USA
[4] City Hope Natl Med Ctr, Dept Hematol Hematopoiet Cell Transplantat, 1500 E Duarte Rd, Duarte, CA 91010 USA
[5] City Hope Natl Med Ctr, Integrat & Genom Core, 1500 E Duarte Rd, Duarte, CA 91010 USA
[6] City Hope Natl Med Ctr, Beckman Res Inst, 1500 E Duarte Rd, Duarte, CA 91010 USA
关键词
TUMOR-INFILTRATING LYMPHOCYTES; INTERNATIONAL-SOCIETY; PROGNOSTIC-FACTORS; LYMPHOMA; PD-L1; MICROENVIRONMENT; ORGANIZATION; ACTIVATION; SURVIVAL; SKIN;
D O I
10.1111/bjd.21063
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
Background The relationship between immune checkpoint status and disease outcome is a major focus of research in cutaneous T-cell lymphoma (CTCL), a disfiguring neoplastic dermatological disorder. Mycosis fungoides (MF) and Sezary syndrome (SS) are the two most common types of CTCL. Objectives The aim was to evaluate the immune checkpoint markers programmed death protein 1 (PD1), inducible T-cell co-stimulator (ICOS) and programmed death-ligand 1 (PD-L1) in skin biopsies from patients with CTCL relative to disease stage and overall survival. Methods This consecutive case series enrolled 47 patients: 57% had stage IA-IIA disease and 43% had stage IIB-IVA2 disease (including seven with SS). Results PD1, PD-L1 and ICOS expression was seen in all biopsies. Notably, PD-L1 was predominantly expressed on histiocytes/macrophages, but focal expression on CTCL cells was seen. High expression of either ICOS or PD-L1 was associated with advanced-stage disease (P = 0 center dot 007 for both) and with the appearance of large-cell transformation (LCT), a histopathological feature associated with a poor prognosis (ICOS: P = 0 center dot 02; PD-L1: P = 0 center dot 002). PD1 expression was not significantly associated with disease stage (P = 0 center dot 12) or LCT (P = 0 center dot 49), but expression was high in SS biopsies. A high combined checkpoint marker score (PD1, PD-L1 and ICOS) was associated with advanced-stage disease (P = 0 center dot 001), LCT (P = 0 center dot 021) and lower overall survival (P = 0 center dot 014). Conclusions These findings demonstrate the existence of a complex immunoregulatory microenvironment in CTCL and support the development of immunotherapies targeting ICOS and PD-L1 in advanced disease.
引用
收藏
页码:234 / 243
页数:10
相关论文
共 50 条
  • [21] Antiprogrammed cell death protein 1 immunotherapy for angiosarcoma with high programmed death-ligand 1 expression: a case report
    Xu, Fei
    Zheng, Jing
    Fu, Mengjiao
    Zhou, Hua
    IMMUNOTHERAPY, 2020, 12 (11) : 771 - 776
  • [22] Variable Expression of Programmed Cell Death Protein 1-Ligand 1 in Kidneys Independent of Immune Checkpoint Inhibition
    Hakroush, Samy
    Kopp, Sarah Birgit
    Tampe, Desiree
    Gersmann, Ann-Kathrin
    Korsten, Peter
    Zeisberg, Michael
    Tampe, Bjorn
    FRONTIERS IN IMMUNOLOGY, 2021, 11
  • [23] Reduced expression of programmed cell death 1 and programmed cell death ligand 1 in infiltrating inflammatory cells of lichen planus without administration of immune checkpoint inhibitors
    Shirouchi, Kazufumi
    Koshikawa, Sachiko
    Shinya, Koichiro
    Watanabe, Hideaki
    Izumi, Miki
    Yoshimura, Kiyoshi
    Sueki, Hirohiko
    JOURNAL OF DERMATOLOGY, 2021, 48 (09): : 1428 - 1432
  • [24] Programmed Cell Death-1: Programmed Cell Death-Ligand 1 Interaction Protects Human Cardiomyocytes Against T-Cell Mediated Inflammation and Apoptosis Response In Vitro
    Tay, Woan Ting
    Fang, Yi-Hsien
    Beh, Suet Theng
    Liu, Yen-Wen
    Hsu, Ling-Wei
    Yen, Chia-Jui
    Liu, Ping-Yen
    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2020, 21 (07)
  • [25] Arbutin overcomes tumor immune tolerance by inhibiting tumor programmed cell death-ligand 1 expression
    Liu, Ching-Han
    Weng, Jing-Ru
    Wu, Li-Hsien
    Song, Rui-Yang
    Huang, Ming-Der
    Wu, Xin-He
    Wang, Chia C.
    Lee, Che-Hsin
    INTERNATIONAL JOURNAL OF MEDICAL SCIENCES, 2024, 21 (15): : 2992 - 3002
  • [26] Tumor necroptosis is correlated with a favorable immune cell signature and programmed death-ligand 1 expression in cholangiocarcinoma
    Thanpisit Lomphithak
    Perawatt Akara-amornthum
    Keigo Murakami
    Masatoshi Hashimoto
    Hajime Usubuchi
    Erina Iwabuchi
    Michiaki Unno
    Zhenyu Cai
    Hironobu Sasano
    Siriporn Jitkaew
    Scientific Reports, 11
  • [27] Differential Immune-Related Microenvironment Determines Programmed Cell Death Protein-1/Programmed Death-Ligand 1 Blockade Efficacy in Patients With Advanced NSCLC
    Shirasawa, Masayuki
    Yoshida, Tatsuya
    Shimoda, Yukiko
    Md, Daisuke Takayanagi
    Shiraishi, Kouya
    Kubo, Takashi
    Mitani, Sachiyo
    Md, Yuji Matsumoto
    Masuda, Ken
    Md, Yuki Shinno
    Md, Yusuke Okuma
    Md, Yasushi Goto
    Md, Hidehito Horinouchi
    Ichikawa, Hitoshi
    Kohno, Takashi
    Md, Noboru Yamamoto
    Md, Shingo Matsumoto
    Md, Koichi Goto
    Md, Shun-ichi Watanabe
    Md, Yuichiro Ohe
    Md, Noriko Motoi
    JOURNAL OF THORACIC ONCOLOGY, 2021, 16 (12) : 2078 - 2090
  • [28] Tumor necroptosis is correlated with a favorable immune cell signature and programmed death-ligand 1 expression in cholangiocarcinoma
    Lomphithak, Thanpisit
    Akara-amornthum, Perawatt
    Murakami, Keigo
    Hashimoto, Masatoshi
    Usubuchi, Hajime
    Iwabuchi, Erina
    Unno, Michiaki
    Cai, Zhenyu
    Sasano, Hironobu
    Jitkaew, Siriporn
    SCIENTIFIC REPORTS, 2021, 11 (01)
  • [29] Expression of Programmed Death-Ligand 1 in Laryngeal Carcinoma and its Effects on Immune Cell Subgroup Infiltration
    Yu, Dan
    Cheng, Jinzhang
    Xue, Kai
    Zhao, Xue
    Wen, Lianji
    Xu, Chengbi
    PATHOLOGY & ONCOLOGY RESEARCH, 2019, 25 (04) : 1437 - 1443
  • [30] The expression of programmed death-ligand 1 and programmed death-ligand 2 in endometrial carcinosarcoma: Correlation with mismatch repair protein expression status, tumor-infiltrating lymphocyte infiltration, and clinical outcomes
    Atilgan, Alev Ok
    Tepeoglu, Merih
    Ozen, Ozlem
    Reyhan, A. Nihan Haberal
    Ayhan, Ali
    ANNALS OF DIAGNOSTIC PATHOLOGY, 2023, 65