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

Morten Orebro Holmström, E. Martinenaite, S. M. Ahmad, Ö. Met, C. Friese, Lasse Kjær, C. H. Riley, P. Thor Straten, I. M. Svane, Hans Karl Hasselbalch, M. H. Andersen

Publikation: Bidrag til tidsskriftArtikelForskningpeer review

Abstrakt

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.

OriginalsprogEngelsk
Sider (fra-til)429-437
Antal sider9
TidsskriftLeukemia
Vol/bind32
Udgave nummer2
DOI
StatusUdgivet - 1 feb. 2018

Fingeraftryk Udforsk hvilke forskningsemner 'The calreticulin (CALR) exon 9 mutations are promising targets for cancer immune therapy' indeholder.

Citationsformater