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Immune checkpoint inhibitors for unresectable or metastatic pleomorphic dermal sarcomas
Pleomorphic dermal sarcomas (PDS) are rare neoplasms of the skin that occur in UV-exposed sites in the elderly, but represent the most common cutaneous sarcomas. Although the majority of PDS can be surgically removed, local recurrences occur in up to 28%, usually occurring within the first two years...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9712951/ https://www.ncbi.nlm.nih.gov/pubmed/36465341 http://dx.doi.org/10.3389/fonc.2022.975342 |
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author | Helbig, Doris Klein, Sebastian |
author_facet | Helbig, Doris Klein, Sebastian |
author_sort | Helbig, Doris |
collection | PubMed |
description | Pleomorphic dermal sarcomas (PDS) are rare neoplasms of the skin that occur in UV-exposed sites in the elderly, but represent the most common cutaneous sarcomas. Although the majority of PDS can be surgically removed, local recurrences occur in up to 28%, usually occurring within the first two years after primary excision. Metastases are diagnosed in up to 20% of cases, mainly observed in the skin, lymph nodes and lungs, preferentially affecting patients with underlying hemato-oncologic diseases. Similar to other UV-induced tumors, PDS are inflammatory and immunogenic tumors (with a high number of CD4+/CD8+ tumor-infiltrating lymphocytes (TILs) and checkpoint molecule expression such as PD-L1, LAG-3, TIGIT) with a very high mutational burden. The most common genetic alterations include UV-induced TP53 loss of function mutations, followed by alterations in the CDKN2A/B gene. Rarely, targetable genetic alterations can be detected. Compelling experimental data and clinical reports about PD-1/PD-L1-blocking antibodies in patients with PDS suggest its use as first line treatment in unresectable or metastatic tumor stages. However, individual („off-line”) patient management should be discussed in an interdisciplinary tumor board based on molecular genetic testing, mutational burden, PD-L1 expression, and evidence of tumor-infiltrating lymphocytes in addition to comorbities of the individual patient. |
format | Online Article Text |
id | pubmed-9712951 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-97129512022-12-02 Immune checkpoint inhibitors for unresectable or metastatic pleomorphic dermal sarcomas Helbig, Doris Klein, Sebastian Front Oncol Oncology Pleomorphic dermal sarcomas (PDS) are rare neoplasms of the skin that occur in UV-exposed sites in the elderly, but represent the most common cutaneous sarcomas. Although the majority of PDS can be surgically removed, local recurrences occur in up to 28%, usually occurring within the first two years after primary excision. Metastases are diagnosed in up to 20% of cases, mainly observed in the skin, lymph nodes and lungs, preferentially affecting patients with underlying hemato-oncologic diseases. Similar to other UV-induced tumors, PDS are inflammatory and immunogenic tumors (with a high number of CD4+/CD8+ tumor-infiltrating lymphocytes (TILs) and checkpoint molecule expression such as PD-L1, LAG-3, TIGIT) with a very high mutational burden. The most common genetic alterations include UV-induced TP53 loss of function mutations, followed by alterations in the CDKN2A/B gene. Rarely, targetable genetic alterations can be detected. Compelling experimental data and clinical reports about PD-1/PD-L1-blocking antibodies in patients with PDS suggest its use as first line treatment in unresectable or metastatic tumor stages. However, individual („off-line”) patient management should be discussed in an interdisciplinary tumor board based on molecular genetic testing, mutational burden, PD-L1 expression, and evidence of tumor-infiltrating lymphocytes in addition to comorbities of the individual patient. Frontiers Media S.A. 2022-11-17 /pmc/articles/PMC9712951/ /pubmed/36465341 http://dx.doi.org/10.3389/fonc.2022.975342 Text en Copyright © 2022 Helbig and Klein https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Helbig, Doris Klein, Sebastian Immune checkpoint inhibitors for unresectable or metastatic pleomorphic dermal sarcomas |
title | Immune checkpoint inhibitors for unresectable or metastatic pleomorphic dermal sarcomas |
title_full | Immune checkpoint inhibitors for unresectable or metastatic pleomorphic dermal sarcomas |
title_fullStr | Immune checkpoint inhibitors for unresectable or metastatic pleomorphic dermal sarcomas |
title_full_unstemmed | Immune checkpoint inhibitors for unresectable or metastatic pleomorphic dermal sarcomas |
title_short | Immune checkpoint inhibitors for unresectable or metastatic pleomorphic dermal sarcomas |
title_sort | immune checkpoint inhibitors for unresectable or metastatic pleomorphic dermal sarcomas |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9712951/ https://www.ncbi.nlm.nih.gov/pubmed/36465341 http://dx.doi.org/10.3389/fonc.2022.975342 |
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