Interplay between Immune Cell Infiltration and Tumor Histological Subtype: A Case of Adrenocortical Cancer

SIMPLE SUMMARY: The interplay between histological subtype and tumor microenvironment, especially the presence of tumor-infiltrating immune cells (TIIC), in adrenocortical cancer remains unclear. Here, we perform a comparative analysis of TIIC composition in conventional and oncocytic histological variants of adrenocortical cancer (ACC) using cases from The Cancer Genome Atlas database and the Endocrinology Research Centre collection (Moscow, Russia) and provide strong evidence that oncocytic ACC is characterized not only by improved survival but also by intensive immune infiltration compared to conventional ACC. Thus, these two histological variants should be independently analyzed to determine the potential role of TIIC in survival and tumor progression. ABSTRACT: The analysis of the tumor microenvironment, especially tumor-infiltrated immune cells, is essential for predicting tumor prognosis, clinical outcomes, and therapy strategies. Adrenocortical cancer is a rare nonimmunogenic malignancy in which the importance of the presence of immune cells is not well understood. In our study, we made the first attempt to understand the interplay between the histology of adrenocortical cancer and its immune landscape using cases from The Cancer Genome Atlas database and the Endocrinology Research Centre collection (Moscow, Russia). We showed that the oncocytic variant of adrenocortical cancer is characterized by intensive immune infiltration and better survival, and it is crucial to analyze the effect of immune infiltration independently for each histological variant.