期刊
LEUKEMIA
卷 32, 期 2, 页码 429-437出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/leu.2017.214
关键词
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资金
- Danish Cancer Society [R90-A6143-14-S2]
- Region Sjaellands Sundhedsvidenskabelige Forskningsfond [12-000095, 15-000342]
- The Danish Cancer Society [R146-A9186, R90-A6143, R72-A4396] Funding Source: researchfish
The calreticulin (CALR) exon 9 mutations are found in similar to 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.
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