Different mechanisms of CD200-CD200R induce diverse outcomes in cancer treatment

被引:3
|
作者
Liao, Kang-Ling [1 ]
Watt, Kenton D. [1 ]
Protin, Tom [2 ]
机构
[1] Univ Manitoba, Dept Math, Winnipeg, MB R3T 2N2, Canada
[2] INSA Rennes, Dept Appl Math, Rennes, France
基金
加拿大自然科学与工程研究理事会;
关键词
Immune checkpoint; CD200-CD200R; PD-1-PD-L1; ODE model; TGF-BETA; DENDRITIC CELLS; MYELOID CELLS; CUTTING EDGE; IFN-GAMMA; T-CELLS; INTERLEUKIN-10; MICROENVIRONMENT; EXPRESSION; INFLAMMATION;
D O I
10.1016/j.mbs.2023.109072
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
The CD200 is a cell membrane protein expressed by tumor cells, and its receptor CD200 receptor (CD200R) is expressed by immune cells including macrophages and dendritic cells. The formation of CD200-CD200R inhibits the cellular functions of the targeted immune cells, so CD200 is one type of the immune checkpoint and blockade CD200-CD200R formation is a potential cancer treatment. However, the CD200 blockade has opposite treatment outcomes in different types of cancers. For instance, the CD200R deficient mice have a higher tumor load than the wild type (WT) mice in melanoma suggesting that CD200-CD200R inhibits melanoma. On the other hand, the antibody anti-CD200 treatment in pancreatic ductal adenocarcinoma (PDAC) and head and neck squamous cell carcinoma (HNSCC) significantly reduces the tumor load indicating that CD200-CD200R promotes PDAC and HNSCC. In this work, we hypothesize that different mechanisms of CD200-CD200R in tumor microenvironment could be one of the reasons for the diverse treatment outcomes of CD200 blockade in different types of cancers. We create one Ordinary Differential Equations (ODEs) model for melanoma including the inhibition of CCL8 and regulatory T cells and the switching from M2 to M1 macrophages by CD200-CD200R to capture the tumor inhibition by CD200-CD200R. We also create another ODEs model for PDAC and HNSCC including the promotion of the polarization and suppressive activities of M2 macrophages by CD200-CD200R to generate the tumor promotion by CD200-CD200R. Furthermore, we use these two models to investigate the treatment efficacy of the combination treatment between the CD200-CD200R blockade and the other immune checkpoint inhibitor, anti-PD-1. Our result shows that different mechanisms of CD200-CD200R can induce different treatment outcomes in combination treatments, namely, only the CD200-CD200R blockade reduces tumor load in melanoma and only the anti-PD-1 and CD200 knockout decrease tumor load in PDAC and HNSCC. Moreover, in melanoma, the CD200-CD200R mainly utilizes the inhibitions on M1 macrophages and dendritic cells to inhibit tumor growth, instead of M2 macrophages.
引用
收藏
页数:32
相关论文
共 50 条
  • [21] The CD200-CD200R Axis Promotes Squamous Cell Carcinoma Metastasis via Regulation of Cathepsin K
    Khan, Iasha Z.
    Del Guzzo, Christina A.
    Shao, Anqi
    Cho, Jiyoon
    Du, Rong
    Cohen, Adrienne O.
    Owens, David M.
    CANCER RESEARCH, 2021, 81 (19) : 5021 - 5032
  • [22] Mathematical Modeling and Analysis of CD200–CD200R in Cancer Treatment
    Kang-Ling Liao
    Kenton D. Watt
    Bulletin of Mathematical Biology, 2022, 84
  • [23] CD200-CD200R dysfunction exacerbates microglial activation and dopaminergic neurodegeneration in a rat model of Parkinson's disease
    Zhang, Shi
    Wang, Xi-Jin
    Tian, Li-Peng
    Pan, Jing
    Lu, Guo-Qiang
    Zhang, Ying-Jie
    Ding, Jian-Qing
    Chen, Sheng-Di
    JOURNAL OF NEUROINFLAMMATION, 2011, 8
  • [24] Characterization and functionality of the CD200-CD200R system during mesenchymal stromal cell interactions with T-lymphocytes
    Najar, Mehdi
    Raicevic, Gordana
    Jebbawi, Fadi
    De Bruyn, Cecile
    Meuleman, Nathalie
    Bron, Dominique
    Toungouz, Michel
    Lagneaux, Laurence
    IMMUNOLOGY LETTERS, 2012, 146 (1-2) : 50 - 56
  • [25] CD200-CD200R轴与疾病的相关性及其研究进展
    徐晗
    毕宇鑫
    李桂霞
    李剑
    王琉丽
    郝瑞家
    郑学敏
    黄瑞晶
    韩进
    李飞
    王根辈
    药学学报, 2024, 59 (04) : 822 - 830
  • [26] CD200-CD200R dysfunction exacerbates microglial activation and dopaminergic neurodegeneration in a rat model of Parkinson's disease
    Shi Zhang
    Xi-Jin Wang
    Li-Peng Tian
    Jing Pan
    Guo-Qiang Lu
    Ying-Jie Zhang
    Jian-Qing Ding
    Sheng-Di Chen
    Journal of Neuroinflammation, 8
  • [27] Brain Innate Immunity in the Regulation of Neuroinflammation: Therapeutic Strategies by Modulating CD200-CD200R Interaction Involve the Cannabinoid System
    Hernangomez, Miriam
    Carrillo-Salinas, Francisco J.
    Mecha, Miriam
    Correa, Fernando
    Mestre, Leyre
    Loria, Frida
    Feliu, Ana
    Docagne, Fabian
    Guaza, Carmen
    CURRENT PHARMACEUTICAL DESIGN, 2014, 20 (29) : 4707 - 4722
  • [28] Exploiting the CD200-CD200R immune checkpoint axis in multiple myeloma to enhance CAR T-cell therapy
    Tang, Yan
    Liu, Wei
    Kadu, Siddhant
    Johnson, Omar
    Hasanali, Zainul S.
    Kelly, Andre
    Shestov, Alexander
    Pajarillo, Raymone
    Greenblatt, Eli
    Holmes, Matthew
    Wang, Li -Ping
    Shih, Natalie
    O'Connor, Roddy S.
    Ruella, Marco
    Garfall, Alfred L.
    Allman, David
    Vogl, Dan T.
    Cohen, Adam
    June, Carl H.
    Sheppard, Neil C.
    BLOOD, 2024, 143 (02) : 139 - 151
  • [29] CD200-CD200R通路在炎症相关性疾病中的研究进展
    丁子玲
    樊毫军
    郭小芹
    吕琪
    中国免疫学杂志, 2025, 41 (02) : 451 - 455
  • [30] Jingfang Granule alleviates bleomycin-induced acute lung injury via CD200-CD200R immunoregulatory pathway
    Lv, Ke
    Li, Mingyue
    Sun, Chenghong
    Miao, Yu
    Zhang, Yan
    Liu, Yang
    Guo, Jianshuang
    Meng, Qing
    Yao, Jingchun
    Zhang, Guimin
    Li, Jing
    JOURNAL OF ETHNOPHARMACOLOGY, 2023, 311