Damage to the major salivary glands is the leading long-term side effect to radiation therapy in patients with head and neck cancerof radiation of head and neck cancers,. It resultresultsing in severe hyposalivationdry mouth , which profoundly impairs basic physiological functions for patients such as speaking, eating, tasting, and swallowing. TodayCurrently, no effective treatment can be offeredexists to alleviate radiation-induced hyposalivation, but recently, treatment with adipose tissue-derived mesenchymal stem/stromal cells (ASC) hasve very recently been tested as a newshowed potential treatment modalityfor restoring the function of the salivary glands. However, the impact of ASC-treatments on the salivary gland proteinome composition has notever been testedinvestigated. HereIn this study, we examine the salivary gland proteomeuse in patients with severe hyposalivation due to radiation therapy and in healthy controls using quantitative metaproteomics. Furthermore, to 1: compare the salivary proteome in patients with severe hyposalivation to that of healthy controls, and 2: towe addresslongitudinally monitorinvestigate the effect of ASC ASC-treatment on the salivary gland proteome. We identify that treatment with ASC-treatments results inis associated with the upregulation of specific proteins in saliva 120 days after injection. Therefore, oOur data findings suggest that ASCs to stimulate biological processes in the salivary gland tissue, which could have beneficial clinical effects.