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[Tumor microenvironment in salivary gland carcinomas: Consequences for new therapeutic concepts]
M F Meyer1, C Arolt2, B A Kansy3
1Klinik für Hals‑, Nasen- und Ohrenheilkunde, Universitätsklinikum Essen, Universität Duisburg-Essen, Hufelandstraße 55, 45147, Essen, Deutschland. moritz.meyer@uk-essen.de.
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.
Insights
Salivary gland carcinomas (SGCs) exhibit diverse tumor microenvironments. The molecule LAG3, an inhibitor of T-cells, is found in aggressive SGCs, suggesting LAG3 inhibition as a potential therapy.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Salivary gland carcinomas (SGCs) are rare and challenging to diagnose and treat due to histological diversity.
- The tumor microenvironment (TME) in SGCs is not well understood, hindering therapeutic advancements.
- Understanding SGC TME could enable improved treatments, including immunomodulation.
Purpose of the Study:
- To review recent studies on the tumor microenvironment composition in salivary gland carcinomas.
- To identify key molecular and immunological factors within the SGC TME.
- To explore potential therapeutic targets based on TME composition.
Main Methods:
- Literature review of studies analyzing SGC tumor microenvironment.
- Analysis of immune cell composition within different SGC subtypes.
- Assessment of cell surface molecule expression on tumor-infiltrating lymphocytes.
Main Results:
- Significant diversity in immune cell composition across SGC entities.
- Lymphocyte-activation gene 3 (LAG3) expression observed in one-third of SGCs.
- Higher LAG3 expression in prognostically unfavorable SGCs like salivary duct carcinomas and adenocarcinomas NOS.
- LAG3, similar to CTLA-4 and PD-1, inhibits anti-tumor T-cell responses.
Conclusions:
- LAG3 is significantly detectable in aggressive and advanced SGCs.
- LAG3 inhibition represents a promising targeted therapy strategy for advanced and metastatic SGCs.
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