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Evidence of immune elimination, immuno-editing and immune escape in patients with hematological cancer

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Holmström, Morten Orebo ; Cordua, Sabrina ; Skov, Vibe ; Kjær, Lasse ; Pallisgaard, Niels ; Ellervik, Christina ; Hasselbalch, Hans Carl ; Andersen, Mads Hald. / Evidence of immune elimination, immuno-editing and immune escape in patients with hematological cancer. I: Cancer immunology, immunotherapy. 2020 ; Bind 69, Nr. 2. s. 315-324.

Bibtex

@article{0a59a79bccd24d4eb7e6ab463b83521f,
title = "Evidence of immune elimination, immuno-editing and immune escape in patients with hematological cancer",
abstract = "There is mounting evidence that the immune system can spontaneously clear malignant lesions before they manifest as overt cancer, albeit this activity has been difficult to demonstrate in humans. The calreticulin (CALR) exon 9 mutations are driver mutations in patients with chronic myeloproliferative neoplasms (MPN), which are chronic blood cancers. The CALR mutations generate a neo-antigen that is recognized by patient T cells, and T cells isolated from a patient with a CALR-mutation can recognize and kill autologous CALR-mutant cells. Surprisingly, healthy individuals display frequent and strong T cell responses to the CALR neo-antigens too. Furthermore, healthy individuals display immune responses to all parts of the mutant CALR epitope, and the CALR neo-epitope specific responses are memory T cell responses. These data suggest that although healthy individuals might acquire a CALR mutation, the mutant cells can be eliminated by the immune system. Additionally, a small fraction of healthy individuals harbor a CALR exon 9 mutation. Four healthy individuals carrying CALR mutations underwent a full medical examination including a bone marrow biopsy after a median follow up of 6.2 years. None of these patients displayed any signs of CALR-mutant MPN. Additionally, all healthy individuals displayed strong CALR neo-epitope specific T cell responses suggesting that these healthy individuals retained their CALR-mutant cells in the editing stage for several years. Thus, we suggest that CALR-mutant MPN could be a disease model of cancer immuno-editing, as we have demonstrated that CALR-mutant MPN displays all three stages described in the theory of cancer immuno-editing.",
keywords = "CALR, CITIM 2019, Immuno-editing, Myeloproliferative neoplasms, Neo-antigen, T cell memory, Hematologic Neoplasms/etiology, Tumor Escape/genetics, Antigens, Neoplasm/immunology, Disease Susceptibility, Epitopes/immunology, Humans, Immunomodulation/genetics, Biomarkers, Tumor, Animals, Cell Transformation, Neoplastic, Mutation, Calreticulin/genetics, Disease Models, Animal",
author = "Holmstr{\"o}m, {Morten Orebo} and Sabrina Cordua and Vibe Skov and Lasse Kj{\ae}r and Niels Pallisgaard and Christina Ellervik and Hasselbalch, {Hans Carl} and Andersen, {Mads Hald}",
year = "2020",
month = feb,
doi = "10.1007/s00262-019-02473-y",
language = "English",
volume = "69",
pages = "315--324",
journal = "Cancer Immunology and Immunotherapy",
issn = "0340-7004",
publisher = "Springer",
number = "2",

}

RIS

TY - JOUR

T1 - Evidence of immune elimination, immuno-editing and immune escape in patients with hematological cancer

AU - Holmström, Morten Orebo

AU - Cordua, Sabrina

AU - Skov, Vibe

AU - Kjær, Lasse

AU - Pallisgaard, Niels

AU - Ellervik, Christina

AU - Hasselbalch, Hans Carl

AU - Andersen, Mads Hald

PY - 2020/2

Y1 - 2020/2

N2 - There is mounting evidence that the immune system can spontaneously clear malignant lesions before they manifest as overt cancer, albeit this activity has been difficult to demonstrate in humans. The calreticulin (CALR) exon 9 mutations are driver mutations in patients with chronic myeloproliferative neoplasms (MPN), which are chronic blood cancers. The CALR mutations generate a neo-antigen that is recognized by patient T cells, and T cells isolated from a patient with a CALR-mutation can recognize and kill autologous CALR-mutant cells. Surprisingly, healthy individuals display frequent and strong T cell responses to the CALR neo-antigens too. Furthermore, healthy individuals display immune responses to all parts of the mutant CALR epitope, and the CALR neo-epitope specific responses are memory T cell responses. These data suggest that although healthy individuals might acquire a CALR mutation, the mutant cells can be eliminated by the immune system. Additionally, a small fraction of healthy individuals harbor a CALR exon 9 mutation. Four healthy individuals carrying CALR mutations underwent a full medical examination including a bone marrow biopsy after a median follow up of 6.2 years. None of these patients displayed any signs of CALR-mutant MPN. Additionally, all healthy individuals displayed strong CALR neo-epitope specific T cell responses suggesting that these healthy individuals retained their CALR-mutant cells in the editing stage for several years. Thus, we suggest that CALR-mutant MPN could be a disease model of cancer immuno-editing, as we have demonstrated that CALR-mutant MPN displays all three stages described in the theory of cancer immuno-editing.

AB - There is mounting evidence that the immune system can spontaneously clear malignant lesions before they manifest as overt cancer, albeit this activity has been difficult to demonstrate in humans. The calreticulin (CALR) exon 9 mutations are driver mutations in patients with chronic myeloproliferative neoplasms (MPN), which are chronic blood cancers. The CALR mutations generate a neo-antigen that is recognized by patient T cells, and T cells isolated from a patient with a CALR-mutation can recognize and kill autologous CALR-mutant cells. Surprisingly, healthy individuals display frequent and strong T cell responses to the CALR neo-antigens too. Furthermore, healthy individuals display immune responses to all parts of the mutant CALR epitope, and the CALR neo-epitope specific responses are memory T cell responses. These data suggest that although healthy individuals might acquire a CALR mutation, the mutant cells can be eliminated by the immune system. Additionally, a small fraction of healthy individuals harbor a CALR exon 9 mutation. Four healthy individuals carrying CALR mutations underwent a full medical examination including a bone marrow biopsy after a median follow up of 6.2 years. None of these patients displayed any signs of CALR-mutant MPN. Additionally, all healthy individuals displayed strong CALR neo-epitope specific T cell responses suggesting that these healthy individuals retained their CALR-mutant cells in the editing stage for several years. Thus, we suggest that CALR-mutant MPN could be a disease model of cancer immuno-editing, as we have demonstrated that CALR-mutant MPN displays all three stages described in the theory of cancer immuno-editing.

KW - CALR

KW - CITIM 2019

KW - Immuno-editing

KW - Myeloproliferative neoplasms

KW - Neo-antigen

KW - T cell memory

KW - Hematologic Neoplasms/etiology

KW - Tumor Escape/genetics

KW - Antigens, Neoplasm/immunology

KW - Disease Susceptibility

KW - Epitopes/immunology

KW - Humans

KW - Immunomodulation/genetics

KW - Biomarkers, Tumor

KW - Animals

KW - Cell Transformation, Neoplastic

KW - Mutation

KW - Calreticulin/genetics

KW - Disease Models, Animal

UR - http://www.scopus.com/inward/record.url?scp=85077561806&partnerID=8YFLogxK

U2 - 10.1007/s00262-019-02473-y

DO - 10.1007/s00262-019-02473-y

M3 - Review

C2 - 31915854

VL - 69

SP - 315

EP - 324

JO - Cancer Immunology and Immunotherapy

JF - Cancer Immunology and Immunotherapy

SN - 0340-7004

IS - 2

ER -

ID: 59227175