Olfactory neuroblastoma (ONB), sinonasal undifferentiated carcinoma (SNUC), and sinonasal neuroendocrine carcinoma (SNEC) are rare malignancies arising from the sinonasal tract with limited therapeutic options. The expression of the somatostatin receptor 2 gene (SSTR2), which is expressed in other neuroendocrine neoplasms and is therapeutically actionable, has been reported in these tumors. Here, we analyzedSSTR2gene expression and its associations with genomic features, established biomarkers predicting of immune response, and the tumor immune microenvironment in a cohort of ONB, SNUC, and SNEC tumor samples (26, 13, and 8 samples, respectively) from a real-world database.SSTR2gene expression was high in neural-type ONB and low in basal-type ONB and in most of the SNUC and SNEC cases; there was no difference in expression between primary and metastatic tumors. The T cell-inflamed (TCI) score analysis classified 38.5% of SNUC cases as T cell-inflamed compared to only 3.9% of ONB and 0% of SNEC cases; 26.9% of ONB cases were classified as intermediate TCI; and SNEC had the lowest relative immune cell infiltration by deconvolution. In highSSTR2-expressing ONB, there was a higher proportion of infiltrating of Natural Killer cells and dendritic cells by deconvolution. Additionally, highSSTR2-expressing ONB was enriched for proliferation pathways, including E2F and Myc targets and G2M checkpoints. In conclusion, our findings delineate significant differences between these three types of sinonasal malignancies that were examined. In ONB, relative to SNUC and SNEC, theSSTR2expression profile, combined with its immune profiles, indicates potential novel therapeutic strategies and combinations for this unmet clinical need. Conversely, the inflammatory microenvironment of SNUC may be targetable using immuno-oncologic therapies.
嗅神经母细胞瘤（ONB）、鼻腔鼻窦未分化癌（SNUC）和鼻腔鼻窦神经内分泌癌（SNEC）是源于鼻腔鼻窦区域的罕见恶性肿瘤，目前治疗手段有限。这些肿瘤中已报道存在生长抑素受体2基因（SSTR2）的表达，该基因在其他神经内分泌肿瘤中亦有表达且具有治疗靶向性。本研究基于真实世界数据库中的ONB、SNUC和SNEC肿瘤样本（分别为26例、13例和8例），分析了SSTR2基因表达及其与基因组特征、已建立的免疫反应预测生物标志物以及肿瘤免疫微环境的关联。结果显示：神经型ONB中SSTR2基因表达较高，而基底型ONB及大多数SNUC和SNEC病例中表达较低；原发灶与转移灶之间的表达无差异。T细胞炎症（TCI）评分分析显示：38.5%的SNUC病例被归类为T细胞炎症型，而ONB和SNEC中该比例分别仅为3.9%和0%；26.9%的ONB病例被归类为中等TCI型；通过反卷积分析发现SNEC的相对免疫细胞浸润程度最低。在高表达SSTR2的ONB中，反卷积分析显示自然杀伤细胞和树突状细胞的浸润比例更高。此外，高表达SSTR2的ONB在增殖通路（包括E2F和Myc靶点以及G2M检查点）中呈现富集。综上所述，本研究结果揭示了这三种鼻腔鼻窦恶性肿瘤之间的显著差异。在ONB中，相对于SNUC和SNEC，SSTR2表达谱结合其免疫特征提示了针对这一未满足临床需求的潜在新型治疗策略和联合治疗方案。相反，SNUC的炎症微环境可能成为免疫肿瘤治疗的潜在靶点。
肿瘤(癌症)患者之家