Spontaneous T-cell responses against the immune check point programmed-death-ligand 1 (PD-L1) in patients with chronic myeloproliferative neoplasms correlate with disease stage and clinical response

Morten Orebo Holmström; Caroline Hasselbalch Riley; Vibe Skov; Inge Marie Svane; Hans Carl Hasselbalch; Mads Hald Andersen

doi:10.1080/2162402X.2018.1433521

Spontaneous T-cell responses against the immune check point programmed-death-ligand 1 (PD-L1) in patients with chronic myeloproliferative neoplasms correlate with disease stage and clinical response

Morten Orebo Holmström
, Caroline Hasselbalch Riley
, Vibe Skov
, Inge Marie Svane
, Hans Carl Hasselbalch
, Mads Hald Andersen^*

^*Corresponding author for this work

Haematology

Research output: Contribution to journal › Article › Research › peer-review

Abstract

The Chronic Myeloproliferative Neoplasms (MPN) are cancers characterized by hyperinflammation and immune deregulation. Concurrently, the expression of the immune check point programmed death ligand 1 (PD-L1) is induced by inflammation. In this study we report on the occurrence of spontaneous T cell responses against a PD-L1 derived epitope in patients with MPN. We show that 71% of patients display a significant immune response against PD-L1, and patients with advanced MPN have significantly fewer and weaker PD-L1 specific immune responses compared to patients with non-advanced MPN. The PD-L1 specific T cell responses are CD4⁺ T cell responses, and by gene expression analysis we show that expression of PD-L1 is enhanced in patients with MPN. This could imply that the tumor specific immune response in MPN could be enhanced by vaccination with PD-L1 derived epitopes by boosting the anti-regulatory immune response hereby allowing tumor specific T cell to exert anti-tumor immunity.

Original language	English
Article number	e1433521
Journal	OncoImmunology
Volume	7
Issue number	6
DOIs	https://doi.org/10.1080/2162402X.2018.1433521
Publication status	Published - 3 Jun 2018

Funding

We thank laboratory technician Merete Jonassen for outstanding help teaching M.O.H to perform the immune cell assays, and the secretaries, nurses and laboratory technicians at Zealand University Hospital for organizing blood draws from patients. This study was supported in part by grant from Kræftens Bekæmpelse to H.C.H (grant number R90-A6143-14-S2) and by grants from Region Sjællands Sundhedsvidenskabelige For-skningsfond to M.O.H (grant numbers 12-000095 and 15-000342). This work was supported by the Region Sjællands Sundhedsvidenskabelige Forskningsfond, 12-000095, Region Sjællands Sundhedsvidenskabelige Forskningsfond, 15-000342, Kræftens Bekæmpelse, R90-A6143-14-S2. This study was supported in part by grant from Danish Cancer Society to H.C.H under grant R90-A6143-14-S2 and by grants from Region Sjællands Sundhedsvidenskabelige Forskningsfond to M.O.H grants 12-000095 and 15-000342 in addition to support from Herlev Hospital.

Keywords

immune check point
immune therapy
Myeloproliferative neoplasms
PD-L1
T cells
vaccination

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10.1080/2162402X.2018.1433521

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Holmström, M. O., Riley, C. H., Skov, V., Svane, I. M., Hasselbalch, H. C., & Andersen, M. H. (2018). Spontaneous T-cell responses against the immune check point programmed-death-ligand 1 (PD-L1) in patients with chronic myeloproliferative neoplasms correlate with disease stage and clinical response. OncoImmunology, 7(6), Article e1433521. https://doi.org/10.1080/2162402X.2018.1433521

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title = "Spontaneous T-cell responses against the immune check point programmed-death-ligand 1 (PD-L1) in patients with chronic myeloproliferative neoplasms correlate with disease stage and clinical response",

abstract = "The Chronic Myeloproliferative Neoplasms (MPN) are cancers characterized by hyperinflammation and immune deregulation. Concurrently, the expression of the immune check point programmed death ligand 1 (PD-L1) is induced by inflammation. In this study we report on the occurrence of spontaneous T cell responses against a PD-L1 derived epitope in patients with MPN. We show that 71\% of patients display a significant immune response against PD-L1, and patients with advanced MPN have significantly fewer and weaker PD-L1 specific immune responses compared to patients with non-advanced MPN. The PD-L1 specific T cell responses are CD4+ T cell responses, and by gene expression analysis we show that expression of PD-L1 is enhanced in patients with MPN. This could imply that the tumor specific immune response in MPN could be enhanced by vaccination with PD-L1 derived epitopes by boosting the anti-regulatory immune response hereby allowing tumor specific T cell to exert anti-tumor immunity.",

keywords = "immune check point, immune therapy, Myeloproliferative neoplasms, PD-L1, T cells, vaccination",

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Holmström, MO, Riley, CH, Skov, V, Svane, IM, Hasselbalch, HC & Andersen, MH 2018, 'Spontaneous T-cell responses against the immune check point programmed-death-ligand 1 (PD-L1) in patients with chronic myeloproliferative neoplasms correlate with disease stage and clinical response', OncoImmunology, vol. 7, no. 6, e1433521. https://doi.org/10.1080/2162402X.2018.1433521

Spontaneous T-cell responses against the immune check point programmed-death-ligand 1 (PD-L1) in patients with chronic myeloproliferative neoplasms correlate with disease stage and clinical response. / Holmström, Morten Orebo; Riley, Caroline Hasselbalch; Skov, Vibe et al.
In: OncoImmunology, Vol. 7, No. 6, e1433521, 03.06.2018.

Research output: Contribution to journal › Article › Research › peer-review

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AU - Holmström, Morten Orebo

AU - Riley, Caroline Hasselbalch

AU - Skov, Vibe

AU - Svane, Inge Marie

AU - Hasselbalch, Hans Carl

AU - Andersen, Mads Hald

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N2 - The Chronic Myeloproliferative Neoplasms (MPN) are cancers characterized by hyperinflammation and immune deregulation. Concurrently, the expression of the immune check point programmed death ligand 1 (PD-L1) is induced by inflammation. In this study we report on the occurrence of spontaneous T cell responses against a PD-L1 derived epitope in patients with MPN. We show that 71% of patients display a significant immune response against PD-L1, and patients with advanced MPN have significantly fewer and weaker PD-L1 specific immune responses compared to patients with non-advanced MPN. The PD-L1 specific T cell responses are CD4+ T cell responses, and by gene expression analysis we show that expression of PD-L1 is enhanced in patients with MPN. This could imply that the tumor specific immune response in MPN could be enhanced by vaccination with PD-L1 derived epitopes by boosting the anti-regulatory immune response hereby allowing tumor specific T cell to exert anti-tumor immunity.

AB - The Chronic Myeloproliferative Neoplasms (MPN) are cancers characterized by hyperinflammation and immune deregulation. Concurrently, the expression of the immune check point programmed death ligand 1 (PD-L1) is induced by inflammation. In this study we report on the occurrence of spontaneous T cell responses against a PD-L1 derived epitope in patients with MPN. We show that 71% of patients display a significant immune response against PD-L1, and patients with advanced MPN have significantly fewer and weaker PD-L1 specific immune responses compared to patients with non-advanced MPN. The PD-L1 specific T cell responses are CD4+ T cell responses, and by gene expression analysis we show that expression of PD-L1 is enhanced in patients with MPN. This could imply that the tumor specific immune response in MPN could be enhanced by vaccination with PD-L1 derived epitopes by boosting the anti-regulatory immune response hereby allowing tumor specific T cell to exert anti-tumor immunity.

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Spontaneous T-cell responses against the immune check point programmed-death-ligand 1 (PD-L1) in patients with chronic myeloproliferative neoplasms correlate with disease stage and clinical response

Abstract

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