High frequencies of circulating memory T cells specific for calreticulin exon 9 mutations in healthy individuals

Morten O Holmström, Shamaila M Ahmad, Uffe Klausen, Simone K Bendtsen, Evelina Martinenaite, Caroline H Riley, Inge M Svane, Lasse Kjær, Vibe Skov, Christina Ellervik, Niels Pallisgaard, Hans C Hasselbalch, Mads H Andersen

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Abstrakt

Mutations in exon 9 of the calreticulin gene (CALR) frequently occur in patients with chronic myeloproliferative neoplasms (MPN). Patients exhibit spontaneous cellular immune responses to epitopes derived from the mutant CALR C-terminus, and CALR-mutant-specific T cells recognize autologous CALR-mutant malignant cells. This study investigated whether CALR-mutant-specific T cells occur naturally in CALRwt MPN-patients and in healthy individuals. Specific immune responses against epitopes in the mutant CALR peptide sequence were detected in both CALRwt MPN-patients and in healthy individuals. Healthy donors displayed more frequent and stronger CALR-mutant specific T-cell responses compared to the responses identified in CALR-mutant MPN-patients. Several T-cell responses were identified in healthy donors directly ex vivo. Importantly, by running functional analyses on live-sorted immune cells from healthy donors, we showed that circulating CALR-mutant-specific immune cells are T-memory cells. These findings suggest, that healthy individuals acquire a CALR exon 9 mutation, but the immune system reacts and clears the mutant cells, and during this reaction generates CALR-mutant specific T-memory cells. We believe that these findings provide the evidence for tumor immune surveillance in MPN.

OriginalsprogEngelsk
Sider (fra-til)8
TidsskriftBlood Cancer Journal
Vol/bind9
Udgave nummer2
DOI
StatusUdgivet - 17 jan. 2019

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