You are here

Article Text

Article menu

Download PDFPDF

E-Poster Presentations
P03 Tumor Microenvironment
P03.24 Calreticulin exposure on malignant blasts correlates with improved NK cell-mediated cytotoxicity in AML patients
Free
  1. I Truxova1,
  2. L Kasikova1,2,
  3. C Salek3,4,
  4. M Hensler1,
  5. D Lysak5,
  6. P Holicek1,2,
  7. P Bilkova1,
  8. M Holubova6,
  9. X Chen7,
  10. R Mikyskova8,
  11. M Reinis8,
  12. M Kovar9,
  13. B Tomalova9,
  14. JP Kline7,10,11,
  15. L Galluzzi12,13,14,15,
  16. R Spisek1,2 and
  17. J Fucikova1,2
  1. 1Sotio a.s, Prague, Czech Republic
  2. 2Department of Immunology, Charles University, 2nd Faculty of Medicine and University Hospital Motol, Prague, Czech Republic
  3. 3Institute of Hematology and Blood Transfusion, Prague, Dominican Republic
  4. 4Institute of Clinical and Experimental Hematology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic
  5. 5Department of Hematology and Oncology, University Hospital in Pilsen, Pilsen, Czech Republic
  6. 6Laboratory of Tumor Biology and Immunotherapy, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic
  7. 7Department of Medicine, University of Chicago, Chicago, IL, USA
  8. 8Laboratory of Immunological and Tumour models, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic
  9. 9Laboratory of Tumor Immunology, Institute of Microbiology of the Czech Academy of Sciences, Prague, Czech Republic
  10. 10Committee on Immunology, University of Chicago, Chicago, Chicago, IL, USA
  11. 11University of Chicago Comprehensive Cancer Center, Chicago, IL, USA
  12. 12Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, USA
  13. 13Sandra and Edward Meyer Cancer Center, New York, NY, USA
  14. 14Caryl and Israel Englander Institute for Precision Medicine, New York, NY, USA
  15. 15Department of Dermatology, Yale School of Medicine, New Haven, CT, USA

Abstract

In some settings, cancer cells responding to treatment undergo an immunogenic form of cell death that is associated with the abundant emission of danger signals in the form of damage-associated molecular patterns. Accumulating preclinical and clinical evidence indicates that danger signals play a crucial role in the (re-)activation of antitumor immune responses in vivo, thus having a major impact on patient prognosis. We have previously demonstrated that the presence of calreticulin on the surface of malignant blasts is a positive prognostic biomarker for patients with acute myeloid leukemia (AML). Calreticulin exposure not only correlated with enhanced T-cell-dependent antitumor immunity in this setting but also affected the number of circulating natural killer (NK) cells upon restoration of normal hematopoiesis. Here, we report that calreticulin exposure on malignant blasts is associated with enhanced NK cell cytotoxic and secretory functions, both in AML patients and in vivo in mice. The ability of calreticulin to stimulate NK-cells relies on CD11c+CD14high cells that, upon exposure to CRT, express higher levels of IL-15Rα, maturation markers (CD86 and HLA- DR) and CCR7. CRT exposure on malignant blasts also correlates with the upregulation of genes coding for type I interferon. This suggests that CD11c+CD14high cells have increased capacity to migrate to secondary lymphoid organs, where can efficiently deliver stimulatory signals (IL-15Rα/IL- 15) to NK cells. These findings delineate a multipronged, clinically relevant mechanism whereby surface-exposed calreticulin favors NK-cell activation in AML patients.

Disclosure Information I. Truxova: None. L. Kasikova: None. C. Salek: None. M. Hensler: None. D. Lysak: None. P. Holicek: None. P. Bilkova: None. M. Holubova: None. X. Chen: None. R. Mikyskova: None. M. Reinis: None. M. Kovar: None. B. Tomalova: None. J.P. Kline: None. L. Galluzzi: None. R. Spisek: None. J. Fucikova: None.

https://doi.org/10.1136/jitc-2020-ITOC7.62

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.