M F Meyer1, C Arolt2, B A Kansy3, J Doescher4, A Quaas2, D Beutner5, S Lang3, J P Klußmann6. 1. Klinik für Hals‑, Nasen- und Ohrenheilkunde, Universitätsklinikum Essen, Universität Duisburg-Essen, Hufelandstraße 55, 45147, Essen, Deutschland. moritz.meyer@uk-essen.de. 2. Institut für Pathologie, Medizinische Fakultät und Uniklinik Köln, Universität zu Köln, Köln, Deutschland. 3. Klinik für Hals‑, Nasen- und Ohrenheilkunde, Universitätsklinikum Essen, Universität Duisburg-Essen, Hufelandstraße 55, 45147, Essen, Deutschland. 4. Klinik für Hals-Nasen-Ohrenheilkunde, Kopf- und Halschirurgie, Universitätsklinikum Ulm, Ulm, Deutschland. 5. Klinik und Poliklinik für Hals‑, Nasen-, und Ohrenheilkunde, Universitätsklinik Göttingen, Göttingen, Deutschland. 6. Klinik und Poliklinik für Hals‑, Nasen- und Ohrenheilkunde, Kopf- und Halschirurgie, Medizinische Fakultät und Uniklinik Köln, Universität zu Köln, Köln, Deutschland.
Abstract
INTRODUCTION: Salivary gland carcinomas (SGCs) are rare tumors which represent a challenge for diagnosis and therapy due to their histological diversity and the different disease courses depending on the respective subtype. Little is known about the composition of the tumor microenvironment in SGCs. A more comprehensive understanding of the relevant molecular changes and immunological processes of the tumor and surrounding stroma could help to improve therapeutic efficiency, for example by adjuvant immunomodulation. METHODS: This manuscript highlights recent studies analyzing the composition of the tumor microenvironment in salivary gland carcinomas. RESULTS: The tumor microenvironment displays a significant diversity in the composition of immune cells among different tumor entities. In one third of the SGCs, an expression of cell surface molecule LAG3 on tumor infiltrating lymphocytes could be observed. LAG3-similar to CTLA‑4 and PD-1-inhibits cellular proliferation, activation, and homeostasis of antitumor-effective T cells. Especially, prognostically less favorable entities such as salivary duct carcinomas and adenocarcinomas NOS (not otherwise specified) yielded higher expressions. CONCLUSIONS: LAG3 is particularly detectable in aggressive entities and advanced tumors. Hence, LAG3 inhibition poses a potential targeted therapy for advanced and metastatic SGCs.
INTRODUCTION: Salivary gland carcinomas (SGCs) are rare tumors which represent a challenge for diagnosis and therapy due to their histological diversity and the different disease courses depending on the respective subtype. Little is known about the composition of the tumor microenvironment in SGCs. A more comprehensive understanding of the relevant molecular changes and immunological processes of the tumor and surrounding stroma could help to improve therapeutic efficiency, for example by adjuvant immunomodulation. METHODS: This manuscript highlights recent studies analyzing the composition of the tumor microenvironment in salivary gland carcinomas. RESULTS: The tumor microenvironment displays a significant diversity in the composition of immune cells among different tumor entities. In one third of the SGCs, an expression of cell surface molecule LAG3 on tumor infiltrating lymphocytes could be observed. LAG3-similar to CTLA‑4 and PD-1-inhibits cellular proliferation, activation, and homeostasis of antitumor-effective T cells. Especially, prognostically less favorable entities such as salivary duct carcinomas and adenocarcinomas NOS (not otherwise specified) yielded higher expressions. CONCLUSIONS: LAG3 is particularly detectable in aggressive entities and advanced tumors. Hence, LAG3 inhibition poses a potential targeted therapy for advanced and metastatic SGCs.
Entities:
Keywords:
Head and neck neoplasms; Immunity, cellular; Immunotherapy; PD‑1; Tumor escape
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