Article

The calreticulin (CALR) exon 9 mutations are promising targets for cancer immune therapy

Leukemia, Springer Nature, ISSN 1476-5551

Volume 32, 2, 2018

DOI:10.1038/leu.2017.214, Dimensions: pub.1090359956, PMID: 28676668,

Authors

Holmström, M O (1) (2)
Met, Ö (1)
Friese, C (1)
Kjær, L (2)
thor Straten, P (1) (4)
Andersen, M H * (1) (4)

* Corresponding author

Affiliations

Organisations

  1. (1) Herlev Hospital, grid.411900.d, Capital Region
  2. (2) Zealand University Hospital, grid.476266.7, Zealand Region
  3. (3) Rigshospitalet, grid.475435.4, Capital Region
  4. (4) University of Copenhagen, grid.5254.6, KU

Countries

Denmark

Continents

Europe

Description

The calreticulin (CALR) exon 9 mutations are found in ∼30% of patients with essential thrombocythemia and primary myelofibrosis. Recently, we reported spontaneous immune responses against the CALR mutations. Here, we describe that CALR-mutant (CALRmut)-specific T cells are able to specifically recognize CALRmut cells. First, we established a T-cell culture specific for a CALRmut epitope. These specific T cells were able to recognize several epitopes in the CALRmut C terminus. Next, we established a CALRmut-specific CD4+ T-cell clone by limiting dilution. These CD4+ T cells recognized autologous CALRmut monocytes and hematopoietic stem cells, and T-cell recognition of target cells was dependent on the presence of CALR. Furthermore, we showed that the CALRmut response was human leukocyte antigen (HLA)-DR restricted. Finally, we demonstrated that the CALRmut-specific CD4+ T cells, despite their phenotype, were cytotoxic to autologous CALRmut cells, and that the cytotoxicity was mediated by degranulation of the T cells. In conclusion, the CALR exon 9 mutations are targets for specific T cells and thus are promising targets for cancer immune therapy such as peptide vaccination in patients harboring CALR exon 9 mutations.

Funders

Research Categories

Main Subject Area

Fields of Research

Links & Metrics

NORA University Profiles

University of Copenhagen

Danish Open Access Indicator

2018: Unused

Research area: Medicine

Danish Bibliometrics Indicator

2018: Level 2

Research area: Medicine

Dimensions Citation Indicators

Times Cited: 32

Field Citation Ratio (FCR): 11.29

Relative Citation ratio (RCR): 4.02