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Age-associated changes in the immune system may influence the response to anti-PD1 therapy in metastatic melanoma patients
Anti-PD1 treatment has improved the survival of metastatic melanoma patients, yet it is unknown which patients benefit from the treatment. In this exploratory study, we aimed to understand the effects of anti-PD1 therapy on the patients’ immune system and discover the characteristics that would resu...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Springer Berlin Heidelberg
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7183505/ https://www.ncbi.nlm.nih.gov/pubmed/32036449 http://dx.doi.org/10.1007/s00262-020-02497-9 |
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author | Kasanen, Henna Hernberg, Micaela Mäkelä, Siru Brück, Oscar Juteau, Susanna Kohtamäki, Laura Ilander, Mette Mustjoki, Satu Kreutzman, Anna |
author_facet | Kasanen, Henna Hernberg, Micaela Mäkelä, Siru Brück, Oscar Juteau, Susanna Kohtamäki, Laura Ilander, Mette Mustjoki, Satu Kreutzman, Anna |
author_sort | Kasanen, Henna |
collection | PubMed |
description | Anti-PD1 treatment has improved the survival of metastatic melanoma patients, yet it is unknown which patients benefit from the treatment. In this exploratory study, we aimed to understand the effects of anti-PD1 therapy on the patients’ immune system and discover the characteristics that would result in successful treatment. We collected peripheral blood (PB) samples from 17 immuno-oncology-naïve metastatic melanoma patients before and after 1 and 3 months of anti-PD1 therapy. In addition, matching tumor biopsies at the time of diagnosis were collected for tissue microarray. The complete blood counts, PB immunophenotype, serum cytokine profiles, and tumor-infiltrating lymphocytes were analyzed and correlated with the clinical data. Patients were categorized based on their disease control into responders (complete response, partial response, stable disease > 6 months, N = 11) and non-responders (progressive disease, stable disease ≤ 6 months, N = 6). During therapy, the PB natural killer T (NKT) cell frequency, expression of CD25 and CD45RO on cytotoxic natural killer (NK) cells, and serum CXC chemokine levels were significantly increased in responders. Furthermore, higher age together with age-associated characteristics from PB, lower frequency of PB-naïve CD8(+) T cells, and elevated levels of serum MCP-4 and OPG were discovered as baseline predictors of treatment response. We therefore propose that in addition to T cells, anti-PD1 treatment is associated with NK- and NKT-cell population dynamics, and that the age-associated characteristics from PB together with older age may contribute to prolonged PFS in anti-PD1-treated melanoma patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00262-020-02497-9) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-7183505 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-71835052020-04-29 Age-associated changes in the immune system may influence the response to anti-PD1 therapy in metastatic melanoma patients Kasanen, Henna Hernberg, Micaela Mäkelä, Siru Brück, Oscar Juteau, Susanna Kohtamäki, Laura Ilander, Mette Mustjoki, Satu Kreutzman, Anna Cancer Immunol Immunother Original Article Anti-PD1 treatment has improved the survival of metastatic melanoma patients, yet it is unknown which patients benefit from the treatment. In this exploratory study, we aimed to understand the effects of anti-PD1 therapy on the patients’ immune system and discover the characteristics that would result in successful treatment. We collected peripheral blood (PB) samples from 17 immuno-oncology-naïve metastatic melanoma patients before and after 1 and 3 months of anti-PD1 therapy. In addition, matching tumor biopsies at the time of diagnosis were collected for tissue microarray. The complete blood counts, PB immunophenotype, serum cytokine profiles, and tumor-infiltrating lymphocytes were analyzed and correlated with the clinical data. Patients were categorized based on their disease control into responders (complete response, partial response, stable disease > 6 months, N = 11) and non-responders (progressive disease, stable disease ≤ 6 months, N = 6). During therapy, the PB natural killer T (NKT) cell frequency, expression of CD25 and CD45RO on cytotoxic natural killer (NK) cells, and serum CXC chemokine levels were significantly increased in responders. Furthermore, higher age together with age-associated characteristics from PB, lower frequency of PB-naïve CD8(+) T cells, and elevated levels of serum MCP-4 and OPG were discovered as baseline predictors of treatment response. We therefore propose that in addition to T cells, anti-PD1 treatment is associated with NK- and NKT-cell population dynamics, and that the age-associated characteristics from PB together with older age may contribute to prolonged PFS in anti-PD1-treated melanoma patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00262-020-02497-9) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2020-02-08 2020 /pmc/articles/PMC7183505/ /pubmed/32036449 http://dx.doi.org/10.1007/s00262-020-02497-9 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Original Article Kasanen, Henna Hernberg, Micaela Mäkelä, Siru Brück, Oscar Juteau, Susanna Kohtamäki, Laura Ilander, Mette Mustjoki, Satu Kreutzman, Anna Age-associated changes in the immune system may influence the response to anti-PD1 therapy in metastatic melanoma patients |
title | Age-associated changes in the immune system may influence the response to anti-PD1 therapy in metastatic melanoma patients |
title_full | Age-associated changes in the immune system may influence the response to anti-PD1 therapy in metastatic melanoma patients |
title_fullStr | Age-associated changes in the immune system may influence the response to anti-PD1 therapy in metastatic melanoma patients |
title_full_unstemmed | Age-associated changes in the immune system may influence the response to anti-PD1 therapy in metastatic melanoma patients |
title_short | Age-associated changes in the immune system may influence the response to anti-PD1 therapy in metastatic melanoma patients |
title_sort | age-associated changes in the immune system may influence the response to anti-pd1 therapy in metastatic melanoma patients |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7183505/ https://www.ncbi.nlm.nih.gov/pubmed/32036449 http://dx.doi.org/10.1007/s00262-020-02497-9 |
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