Cargando…
Dexamethasone differentially depletes tumour and peripheral blood lymphocytes and can impact the efficacy of chemotherapy/checkpoint blockade combination treatment
Dexamethasone is a synthetic glucocorticoid commonly used for the prevention and management of side effects in cancer patients undergoing chemotherapy. While it is effective as an anti-emetic and in preventing hypersensitivity reactions, dexamethasone depletes peripheral blood lymphocytes and impact...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6791454/ https://www.ncbi.nlm.nih.gov/pubmed/31646089 http://dx.doi.org/10.1080/2162402X.2019.1641390 |
_version_ | 1783458981473157120 |
---|---|
author | Aston, Wayne J. Hope, Danika E. Cook, Alistair M. Boon, Louis Dick, Ian Nowak, Anna K. Lake, Richard A. Lesterhuis, W. Joost |
author_facet | Aston, Wayne J. Hope, Danika E. Cook, Alistair M. Boon, Louis Dick, Ian Nowak, Anna K. Lake, Richard A. Lesterhuis, W. Joost |
author_sort | Aston, Wayne J. |
collection | PubMed |
description | Dexamethasone is a synthetic glucocorticoid commonly used for the prevention and management of side effects in cancer patients undergoing chemotherapy. While it is effective as an anti-emetic and in preventing hypersensitivity reactions, dexamethasone depletes peripheral blood lymphocytes and impacts immune responses. The effect of dexamethasone on the number and quality of tumour-infiltrating leukocytes has not been reported. To address this, we calibrated the dose in two different strains of mice to achieve the same extent of peripheral blood lymphocyte depletion observed in patients with cancer. Doses that caused analogous depletion of T and B lymphocytes and NK cells from the peripheral blood, elicited no change in these populations within the tumour. The expression of immune checkpoint molecules PD-1, OX40, GITR and TIM3 on tumour-infiltrating lymphocytes was not altered. We found that dexamethasone had a small but significant deleterious impact on weakly efficacious chemoimmunotherapy but had no effect when the protocol was highly efficacious. Based on these results, we predict that dexamethasone will have a modest negative influence on the overall effectiveness of chemoimmunotherapy treatment. |
format | Online Article Text |
id | pubmed-6791454 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-67914542019-10-23 Dexamethasone differentially depletes tumour and peripheral blood lymphocytes and can impact the efficacy of chemotherapy/checkpoint blockade combination treatment Aston, Wayne J. Hope, Danika E. Cook, Alistair M. Boon, Louis Dick, Ian Nowak, Anna K. Lake, Richard A. Lesterhuis, W. Joost Oncoimmunology Original Research Dexamethasone is a synthetic glucocorticoid commonly used for the prevention and management of side effects in cancer patients undergoing chemotherapy. While it is effective as an anti-emetic and in preventing hypersensitivity reactions, dexamethasone depletes peripheral blood lymphocytes and impacts immune responses. The effect of dexamethasone on the number and quality of tumour-infiltrating leukocytes has not been reported. To address this, we calibrated the dose in two different strains of mice to achieve the same extent of peripheral blood lymphocyte depletion observed in patients with cancer. Doses that caused analogous depletion of T and B lymphocytes and NK cells from the peripheral blood, elicited no change in these populations within the tumour. The expression of immune checkpoint molecules PD-1, OX40, GITR and TIM3 on tumour-infiltrating lymphocytes was not altered. We found that dexamethasone had a small but significant deleterious impact on weakly efficacious chemoimmunotherapy but had no effect when the protocol was highly efficacious. Based on these results, we predict that dexamethasone will have a modest negative influence on the overall effectiveness of chemoimmunotherapy treatment. Taylor & Francis 2019-07-13 /pmc/articles/PMC6791454/ /pubmed/31646089 http://dx.doi.org/10.1080/2162402X.2019.1641390 Text en © 2019 The Author(s). Published with license by Taylor & Francis Group, LLC. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way. |
spellingShingle | Original Research Aston, Wayne J. Hope, Danika E. Cook, Alistair M. Boon, Louis Dick, Ian Nowak, Anna K. Lake, Richard A. Lesterhuis, W. Joost Dexamethasone differentially depletes tumour and peripheral blood lymphocytes and can impact the efficacy of chemotherapy/checkpoint blockade combination treatment |
title | Dexamethasone differentially depletes tumour and peripheral blood lymphocytes and can impact the efficacy of chemotherapy/checkpoint blockade combination treatment |
title_full | Dexamethasone differentially depletes tumour and peripheral blood lymphocytes and can impact the efficacy of chemotherapy/checkpoint blockade combination treatment |
title_fullStr | Dexamethasone differentially depletes tumour and peripheral blood lymphocytes and can impact the efficacy of chemotherapy/checkpoint blockade combination treatment |
title_full_unstemmed | Dexamethasone differentially depletes tumour and peripheral blood lymphocytes and can impact the efficacy of chemotherapy/checkpoint blockade combination treatment |
title_short | Dexamethasone differentially depletes tumour and peripheral blood lymphocytes and can impact the efficacy of chemotherapy/checkpoint blockade combination treatment |
title_sort | dexamethasone differentially depletes tumour and peripheral blood lymphocytes and can impact the efficacy of chemotherapy/checkpoint blockade combination treatment |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6791454/ https://www.ncbi.nlm.nih.gov/pubmed/31646089 http://dx.doi.org/10.1080/2162402X.2019.1641390 |
work_keys_str_mv | AT astonwaynej dexamethasonedifferentiallydepletestumourandperipheralbloodlymphocytesandcanimpacttheefficacyofchemotherapycheckpointblockadecombinationtreatment AT hopedanikae dexamethasonedifferentiallydepletestumourandperipheralbloodlymphocytesandcanimpacttheefficacyofchemotherapycheckpointblockadecombinationtreatment AT cookalistairm dexamethasonedifferentiallydepletestumourandperipheralbloodlymphocytesandcanimpacttheefficacyofchemotherapycheckpointblockadecombinationtreatment AT boonlouis dexamethasonedifferentiallydepletestumourandperipheralbloodlymphocytesandcanimpacttheefficacyofchemotherapycheckpointblockadecombinationtreatment AT dickian dexamethasonedifferentiallydepletestumourandperipheralbloodlymphocytesandcanimpacttheefficacyofchemotherapycheckpointblockadecombinationtreatment AT nowakannak dexamethasonedifferentiallydepletestumourandperipheralbloodlymphocytesandcanimpacttheefficacyofchemotherapycheckpointblockadecombinationtreatment AT lakericharda dexamethasonedifferentiallydepletestumourandperipheralbloodlymphocytesandcanimpacttheefficacyofchemotherapycheckpointblockadecombinationtreatment AT lesterhuiswjoost dexamethasonedifferentiallydepletestumourandperipheralbloodlymphocytesandcanimpacttheefficacyofchemotherapycheckpointblockadecombinationtreatment |