Tumor microenvironment in salivary gland carcinomas: Consequences for new therapeutic concepts

Abstract

Salivary gland carcinomas (SGCs) are rare tumors which represent achallenge 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. Amore 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. This manuscript highlights recent studies analyzing the composition of the tumor microenvironment in salivary gland carcinomas. The tumor microenvironment displays asignificant 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 Tcells. Especially, prognostically less favorable entities such as salivary duct carcinomas and adenocarcinomas NOS (not otherwise specified) yielded higher expressions. LAG3 is particularly detectable in aggressive entities and advanced tumors. Hence, LAG3 inhibition poses apotential targeted therapy for advanced and metastatic SGCs.