The understanding of the mechanisms underlying thyroid cancer immune escape can lead to the identification of new molecular targets and/or efficacy biomarkers. For this purpose, we performed immune expression profiling in thyroid cancers to obtain a comprehensive view on immune mechanisms activated during cancer progression. The study was conducted retrospectively in 25 papillary thyroid carcinomas (PTCs), 14 poorly differentiated thyroid carcinomas (PDTC), 13 anaplastic thyroid carcinomas (ATCs), and 7 normal thyroid (NT) tissue samples. Gene expression profiling was obtained on RNA samples using the Nanostring platform and its nCounter PanCancer Immune Profiling Panel. Gene expression comparison of ATC, PTC, and PDTC vs NT showed high number of regulated genes in cancer samples. In detail, immune-related gene sets were significantly upregulated (ATC > PTC > > PDTC). Most ATC and approximately half of PTC showed a microenvironment infiltrated by macrophages and T-cells with CD8+ effector phenotype, part of which appeared to be functionally exhausted. Conversely, most PDTC, as NT samples, as the remaining part of PTC, displayed a poor or absent infiltration by immune cells. Interestingly, an upregulation of inhibitory immune checkpoint mediators, including PDL1, PDL2, PD1, LAG-3, TIM-3, PVR, and TIGIT, could be detected in ATC and PTC. These data indicated the existence of two major immune phenotypes in thyroid carcinoma: an ATC-like one, including hot and altered-immunosuppressed tumors and a PDTC-like one, including altered-excluded and cold tumors. Confirmation of the findings in locally advanced or metastatic cancer tissues is expected to have important immunotherapeutic implications.

Background/Objectives: Salvia officinalis L. is widely used in food supplements, particularly those intended to support women’s health and alleviate menopausal vasomotor symptoms. However, the extent to which estrogen receptor signaling contributes to its reported clinical benefits remains unclear. Therefore, evaluating its potential endocrine activity is a key aspect of its toxicological characterization and overall safety assessment. The present study aimed to investigate the potential estrogenic effects of a standardized Italian Salvia officinalis L. extract (Salvira™), as well as its biological effects on estrogen-responsive breast cancer cells (MCF-7). Methods: In vitro enzymatic assays and estrogen receptor alpha (ERα) agonist- and antagonist-mode experiments were performed to assess its ability to modulate ERα signaling. Moreover, cell viability, proliferation, and clonogenic capacity were assessed in MCF-7 cells following exposure to increasing concentrations of the extract. Results: The extract did not exhibit estrogenic activity in all experimental dose–response assays. In MCF-7 cells, treatment with the sage extract did not produce an overall effect on cell viability or proliferative capacity. Moreover, no impairment of long-term clonogenic potential was observed at the tested concentrations. Conclusions: Under the experimental conditions investigated, the present findings suggest that the standardized Salvia officinalis L. extract showed no evidence of estrogenic activity and did not induce relevant ERα-mediated biological effects in estrogen-responsive MCF-7 cells. These findings contribute to the characterization of the endocrine safety profile of the extract, supporting its safe use as an ingredient in food supplements.