Functional expression of CD73 on human natural killer cells

被引:0
|
作者
Andrea M. Chambers
Jiao Wang
Tram N. Dao
Kyle B. Lupo
Paige Veenhuis
Mitchell G. Ayers
Veronika Slivova
Aaron A. Cohen-Gadol
Sandro Matosevic
机构
[1] Purdue University,Department of Industrial and Physical Pharmacy
[2] Purdue University,Department of Medicinal Chemistry and Molecular Pharmacology
[3] Indiana University Health,Enterprise Clinical Research Operations Biorepository
[4] Indiana University,Department of Neurological Surgery
[5] Purdue University,Center for Cancer Research
来源
Cancer Immunology, Immunotherapy | 2022年 / 71卷
关键词
NK cells; CD73; Tumor microenvironment; Immunometabolism; Adenosine;
D O I
暂无
中图分类号
学科分类号
摘要
The production of adenosine by CD73 on cancer cells in the tumor microenvironment is a recognized immunosuppressive mechanism contributing to immune evasion in many solid tumors. While NK cells have been purported to overexpress CD73 under certain conditions, this phenomenon has remained elusive and unclear. We have found that while NK cells are able to upregulate expression of CD73 on their surface when exposed to CD73+ cancer cells, this upregulation is not universal, nor is it often substantial. Rather, our data point to the extent of CD73 expression on NK cells to be both cancer-specific and environmentally-driven, and largely limited in intensity. We found that NK cell overexpression of CD73 responds to the level of CD73 on cancer cells and is enhanced in hypoxia. Interestingly, human CD73+ NK cells appear hyperfunctional in vitro compared to CD73− NK cells, suggesting that CD73 expression could be a bystander of NK cell activation. In addition, glioblastoma patient data show that tumor-infiltrating NK cells express CD73 variably, depending on donor, and present lower expression of CD16, alongside patient-specific changes in CEACAM1, CXCR3 and TIM-3, suggesting some functional changes in NK cell responses associated with expression of CD73 on NK cells in vivo. Taken together, our study is the first to show that while NK cells are largely resistant to the upregulation of CD73, CD73 expression is inducible on NK cells in response to CD73 on cancer cells, and these cells are associated with distinct functional signatures.
引用
收藏
页码:3043 / 3056
页数:13
相关论文
共 50 条
  • [31] Expression and regulation of complement receptors by human natural killer cells
    Min, Xiaoyun
    Liu, Chengfei
    Wei, Yang
    Wang, Na
    Yuan, Guolian
    Liu, Dan
    Li, Zongfang
    Zhou, Wuding
    Li, Ke
    IMMUNOBIOLOGY, 2014, 219 (09) : 671 - 679
  • [32] Expression and activity of extracellular ectoenzymes (CD39 and CD73) in aortic valves cells and in endothelial cells under the shear stress conditions
    Kaniewska, E. D.
    Sielicka, A.
    Sarathchandra, P.
    Pelikant-Malecka, I.
    Chester, A. H.
    Yacoub, M. H.
    Smolenski, R. T.
    FEBS JOURNAL, 2014, 281 : 561 - 562
  • [33] CD11b and CD27 reflect distinct population and functional specialization in human natural killer cells
    Fu, Binqing
    Wang, Fuyan
    Sun, Rui
    Ling, Bin
    Tian, Zhigang
    Wei, Haiming
    IMMUNOLOGY, 2011, 133 (03) : 350 - 359
  • [34] A three-dimensional microenvironment alters CD73 expression in cervical cancer
    Iser, Isabele Cristiana
    de Andrade Mello, Paola
    Davies, Samuel
    de Souza Santos, Jacqueline Fraga
    Pilger, Diogo Andre
    Buffon, Andreia
    Bertoni, Ana Paula Santin
    Wink, Marcia Rosangela
    CELL BIOCHEMISTRY AND FUNCTION, 2021, 39 (06) : 780 - 790
  • [35] Prognostic significance and immune correlates of CD73 expression in renal cell carcinoma
    Tripathi, Abhishek
    Lin, Edwin
    Xie, Wanling
    Flaifel, Abdallah
    Steinharter, John A.
    Stern Gatof, Emily N.
    Bouchard, Gabrielle
    Fleischer, Justin H.
    Martinez-Chanza, Nieves
    Gray, Connor
    Mantia, Charlene
    Thompson, Linda
    Wei, Xiao X.
    Giannakis, Marios
    McGregor, Bradley A.
    Choueiri, Toni K.
    Agarwal, Neeraj
    McDermott, David F.
    Signoretti, Sabina
    Harshman, Lauren C.
    JOURNAL FOR IMMUNOTHERAPY OF CANCER, 2020, 8 (02)
  • [36] Prognostic value of CD73 expression in resected colorectal cancer liver metastasis
    Messaoudi, Nouredin
    Cousineau, Isabelle
    Arslanian, Elizabeth
    Henault, David
    Stephen, David
    Vandenbroucke-Menu, Franck
    Dagenais, Michel
    Letourneau, Richard
    Plasse, Marylene
    Roy, Andre
    Lapointe, Real
    Ysebaert, Dirk
    Trudel, Dominique
    Soucy, Genevieve
    Stagg, John
    Turcotte, Simon
    ONCOIMMUNOLOGY, 2020, 9 (01):
  • [37] CD73 expression in lymph node metastases in patients with head and neck cancer
    Mandapathil, Magis
    Boduc, Mehtap
    Netzer, Christoph
    Gueldner, Christian
    Roessler, Marion
    Wallicek-Dworschak, Ute
    Jahns, Evelyn
    Stuck, Boris
    ACTA OTO-LARYNGOLOGICA, 2018, 138 (02) : 180 - 184
  • [38] Proteasome inhibitors reduce CD73 expression partly via decreasing p-ERK in NSCLC cells
    Su, Ai-Ling
    Tian, Chang-Qing
    Ou, Ying-Jie
    Bao, Xu-Bin
    Huan, Xia-Juan
    Miao, Ze-Hong
    Wang, Ying-Qing
    LIFE SCIENCES, 2023, 332
  • [39] Discovery of natural product ellagic acid as a potent CD73 and CD39 dual inhibitor
    Wang, Yuan
    Wang, Chuanhao
    Zhu, Yazhao
    Zhang, Yanming
    Chen, Baobao
    Wu, Yuelin
    Yao, Jianzhong
    Miao, Zhenyuan
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2021, 34
  • [40] Targeting CD73 in the tumor microenvironment with MEDI9447
    Hay, Carl M.
    Sult, Erin
    Huang, Qihui
    Mulgrew, Kathy
    Fuhrmann, Stacy R.
    McGlinchey, Kelly A.
    Hammond, Scott A.
    Rothstein, Raymond
    Rios-Doria, Jonathan
    Poon, Edmund
    Holoweckyj, Nick
    Durham, Nicholas M.
    Leow, Ching Ching
    Diedrich, Gundo
    Damschroder, Melissa
    Herbst, Ronald
    Hollingsworth, Robert E.
    Sachsenmeier, Kris F.
    ONCOIMMUNOLOGY, 2016, 5 (08):