Anti-PD-1 antibody decreases tumour-infiltrating regulatory T cells

被引:84
|
作者
Yoshida, Kazushige [1 ]
Okamoto, Masanori [1 ]
Sasaki, Jun [1 ]
Kuroda, Chika [2 ]
Ishida, Haruka [2 ]
Ueda, Katsuya [2 ]
Ideta, Hirokazu [1 ]
Kamanaka, Takayuki [1 ]
Sobajima, Atsushi [1 ]
Takizawa, Takashi [1 ]
Tanaka, Manabu [3 ]
Aoki, Kaoru [4 ]
Uemura, Takeshi [2 ]
Kato, Hiroyuki [1 ]
Haniu, Hisao [2 ]
Saito, Naoto [2 ]
机构
[1] Shinshu Univ, Dept Orthopaed Surg, Sch Med, Matsumoto, Nagano, Japan
[2] Shinshu Univ, Inst Biomed Sci, Interdisciplinary Cluster Cutting Edge Res, Asahi 3-1-1, Matsumoto, Nagano 3908621, Japan
[3] Okaya City Hosp, Dept Orthoped Surg, Okaya, Japan
[4] Shinshu Univ, Sch Hlth Sci, Phys Therapy Div, Sch Med, Matsumoto, Nagano, Japan
关键词
PD-1; Treg; Osteosarcoma; Anti-PD-1; antibody; IFN-GAMMA; CANCER; PD-L1; BLOCKADE; EXPRESSION; SUPPRESSION; EFFICACY; THERAPY; ROLES; FOXP3;
D O I
10.1186/s12885-019-6499-y
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background There are many types of therapies for cancer. In these days, immunotherapies, especially immune checkpoint inhibitors, are focused on. Though many types of immune checkpoint inhibitors are there, the difference of effect and its mechanism are unclear. Some reports suggest the response rate of anti-PD-1 antibody is superior to that of anti-PD-L1 antibody and could potentially produce different mechanisms of action. On the other hand, Treg also express PD-1; however, their relationship remains unclear. Methods In this study, we used osteosarcoma cell lines in vitro and osteosarcoma mouse model in vivo. In vitro, we analyzed the effect of IFN gamma for expression of PD-L1 on the surface of cell lines by flowcytometry. In vivo, murine osteosarcoma cell line LM8 was subcutaneously transplanted into the dorsum of mice. Mouse anti-PD-1 antibody was intraperitoneally administered. we analysed the effect for survival of anti-PD-1 antibody and proportion of T cells in the tumour by flowcytometry. Results We discovered that IFN gamma increased PD-L1 expression on the surface of osteosarcoma cell lines. In assessing the relationship between anti-PD-1 antibody and Treg, we discovered the administration of anti-PD-1 antibody suppresses increases in tumour volume and prolongs overall survival time. In the tumour microenvironment, we found that the administration of anti-PD-1 antibody decreased Treg within the tumour and increased tumour-infiltrating lymphocytes. Conclusions Here we clarify for the first time an additional mechanism of anti-tumour effect-as exerted by anti-PD-1 antibody decreasing Treg- we anticipate that our findings will lead to the development of new methods for cancer treatment.
引用
收藏
页数:10
相关论文
共 50 条
  • [21] Anti-PD-1 Checkpoint Therapy Can Promote the Function and Survival of Regulatory T Cells
    Vick, Sarah C.
    Kolupaev, Oleg, V
    Perou, Charles M.
    Serody, Jonathan S.
    JOURNAL OF IMMUNOLOGY, 2021, 207 (10): : 2598 - 2607
  • [22] In vitro preliminary study on different anti-PD-1 antibody concentrations on T cells activation
    Irena Wieleba
    Kamila Wojas-Krawczyk
    Izabela Chmielewska
    Magdalena Wójcik-Superczyńska
    Paweł Krawczyk
    Janusz Milanowski
    Scientific Reports, 12
  • [23] In vitro preliminary study on different anti-PD-1 antibody concentrations on T cells activation
    Wieleba, Irena
    Wojas-Krawczyk, Kamila
    Chmielewska, Izabela
    Wojcik-Superczynska, Magdalena
    Krawczyk, Pawel
    Milanowski, Janusz
    SCIENTIFIC REPORTS, 2022, 12 (01)
  • [24] Tumour-infiltrating regulatory T cells stimulate mammary cancer metastasis through RANKL-RANK signalling
    Tan, Wei
    Zhang, Weizhou
    Strasner, Amy
    Grivennikov, Sergei
    Cheng, Jin Q.
    Hoffman, Robert M.
    Karin, Michael
    NATURE, 2011, 470 (7335) : 548 - 553
  • [25] Anti-PD-1 antibody armored γδ T cells enhance anti-tumor efficacy in ovarian cancer
    Yue Wang
    Jingyi Han
    Dongdong Wang
    Menghua Cai
    Yi Xu
    Yu Hu
    Hui Chen
    Wei He
    Jianmin Zhang
    Signal Transduction and Targeted Therapy, 8
  • [26] ImmTAC/Anti-PD-1 antibody combination to enhance killing of cancer cells by reversing regulatory T-cell-mediated immunosuppression
    Zhang, Huanling
    Li, Yanyan
    Liu, Xiaoping
    Liang, Zhaoduan
    Yan, Mengyong
    Liu, Qiang
    Chen, Anan
    Bao, Yifeng
    Zhou, Chengzhi
    Li, Shiyue
    Yee, Cassian
    Li, Yi
    IMMUNOLOGY, 2018, 155 (02) : 238 - 250
  • [27] Anti-PD-1 antibody armored γδ T cells enhance anti-tumor efficacy in ovarian cancer
    Wang, Yue
    Han, Jingyi
    Wang, Dongdong
    Cai, Menghua
    Xu, Yi
    Hu, Yu
    Chen, Hui
    He, Wei
    Zhang, Jianmin
    SIGNAL TRANSDUCTION AND TARGETED THERAPY, 2023, 8 (01)
  • [28] Therapeutic depletion of CCR8+ tumor-infiltrating regulatory T cells elicits antitumor immunity and synergizes with anti-PD-1 therapy
    Van Damme, Helena
    Dombrecht, Bruno
    Kiss, Mate
    Roose, Heleen
    Allen, Elizabeth
    Van Overmeire, Eva
    Kancheva, Daliya
    Martens, Liesbet
    Murgaski, Aleksandar
    Bardet, Pauline Madeleine Rachel
    Blancke, Gillian
    Jans, Maude
    Bolli, Evangelia
    Martins, Maria Solange
    Elkrim, Yvon
    Dooley, James
    Boon, Louis
    Schwarze, Julia Katharina
    Tacke, Frank
    Movahedi, Kiavash
    Vandamme, Niels
    Neyns, Bart
    Ocak, Sebahat
    Scheyltjens, Isabelle
    Vereecke, Lars
    Nana, Frank Aboubakar
    Merchiers, Pascal
    Laoui, Damya
    Van Ginderachter, Jo Agnes
    JOURNAL FOR IMMUNOTHERAPY OF CANCER, 2021, 9 (02)
  • [29] Anti-PD-1 antibody treatment for melanoma
    Ribas, Antoni
    Kirkwood, John M.
    Flaherty, Keith T.
    LANCET ONCOLOGY, 2018, 19 (05): : E219 - E219
  • [30] Tumor-infiltrating mast cells are associated with resistance to anti-PD-1 therapy
    Rajasekharan Somasundaram
    Thomas Connelly
    Robin Choi
    Hyeree Choi
    Anastasia Samarkina
    Ling Li
    Elizabeth Gregorio
    Yeqing Chen
    Rohit Thakur
    Mohamed Abdel-Mohsen
    Marilda Beqiri
    Meaghan Kiernan
    Michela Perego
    Fang Wang
    Min Xiao
    Patricia Brafford
    Xue Yang
    Xiaowei Xu
    Anthony Secreto
    Gwenn Danet-Desnoyers
    Daniel Traum
    Klaus H. Kaestner
    Alexander C. Huang
    Denitsa Hristova
    Joshua Wang
    Mizuho Fukunaga-Kalabis
    Clemens Krepler
    Fang Ping-Chen
    Xiangyang Zhou
    Alexis Gutierrez
    Vito W. Rebecca
    Prashanthi Vonteddu
    Farokh Dotiwala
    Shashi Bala
    Sonali Majumdar
    Harsh Dweep
    Jayamanna Wickramasinghe
    Andrew V. Kossenkov
    Jorge Reyes-Arbujas
    Kenisha Santiago
    Tran Nguyen
    Johannes Griss
    Frederick Keeney
    James Hayden
    Brian J. Gavin
    David Weiner
    Luis J. Montaner
    Qin Liu
    Lukas Peiffer
    Jürgen Becker
    Nature Communications, 12