TUMOR MICROENVIRONMENT IN ADENOID CYSTIC CARCINOMAS OF SALIVARY GLANDS: A COMPREHENSIVE REVIEW

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Objectives Adenoid cystic carcinoma (AdCC) is the second most common salivary gland tumor, accounting for approximately 10% of cases. The aim was to review the tumor microenvironment (TME) components of AdCC and how it regulates tumor progression and the use of candidate targets for AdCC therapy. Study Design A language database search was performed retrieving studies that evaluated the TME of AdCC by different methodologies. Results The findings support the fact that the tumor microenvironment of AdCC, as in other cancers, is composed of a heterogeneous network of interactions involving immune cells (T and B lymphocytes and NK) and their immune checkpoints (especially PD1, PD-L1, and CTLA-4), extracellular matrix production and its inhibitors (MMP-2, MMP-9 e TIMP-1), production of cytokines, chemokines, and growth factors (IL-6, IL-8 CCX4, and FGF-2) and cancer-associated fibroblasts. Taken together, they may promote cell growth and development by inhibition of antitumor responses, induction of angiogenesis, and metastasis. Conclusions TME of AdCC shows complex interactions that leads to a protumoral microenvironment and a poor prognosis. Also, immune cells are potential targets for immune therapy in these tumors. Adenoid cystic carcinoma (AdCC) is the second most common salivary gland tumor, accounting for approximately 10% of cases. The aim was to review the tumor microenvironment (TME) components of AdCC and how it regulates tumor progression and the use of candidate targets for AdCC therapy. A language database search was performed retrieving studies that evaluated the TME of AdCC by different methodologies. The findings support the fact that the tumor microenvironment of AdCC, as in other cancers, is composed of a heterogeneous network of interactions involving immune cells (T and B lymphocytes and NK) and their immune checkpoints (especially PD1, PD-L1, and CTLA-4), extracellular matrix production and its inhibitors (MMP-2, MMP-9 e TIMP-1), production of cytokines, chemokines, and growth factors (IL-6, IL-8 CCX4, and FGF-2) and cancer-associated fibroblasts. Taken together, they may promote cell growth and development by inhibition of antitumor responses, induction of angiogenesis, and metastasis. TME of AdCC shows complex interactions that leads to a protumoral microenvironment and a poor prognosis. Also, immune cells are potential targets for immune therapy in these tumors.