Universität zu Köln

Helbig, Doris and Klein, Sebastian (2022). Immune checkpoint inhibitors for unresectable or metastatic pleomorphic dermal sarcomas. Front. Oncol., 12. LAUSANNE: FRONTIERS MEDIA SA. ISSN 2234-943X

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Abstract

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Helbig, Doris UNSPECIFIED UNSPECIFIED UNSPECIFIED Klein, Sebastian UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-668116
DOI:	10.3389/fonc.2022.975342
Journal or Publication Title:	Front. Oncol.
Volume:	12
Date:	2022
Publisher:	FRONTIERS MEDIA SA
Place of Publication:	LAUSANNE
ISSN:	2234-943X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language DERMATOFIBROSARCOMA PROTUBERANS; ATYPICAL FIBROXANTHOMAS; THERAPEUTIC TARGET; CTLA-4 BLOCKADE; PD-1 BLOCKADE; IMATINIB; MUTATIONS; RESISTANT; FREQUENT Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/66811