PDF(Pubmed)
Abstract：
BACKGROUND: Olfactory neuroblastoma is a rare malignancy of the anterior skull base typically treated with surgery and adjuvant radiation. Although outcomes are fair for low-grade disease, patients with high-grade, recurrent, or metastatic disease oftentimes respond poorly to standard treatment methods. We hypothesized that an in-depth evaluation of the olfactory neuroblastoma tumor immune microenvironment would identify mechanisms of immune evasion in high-grade olfactory neuroblastoma as well as rational targetable mechanisms for future translational immunotherapeutic approaches.
METHODS: Multispectral immunofluorescence and RNAScope evaluation of the tumor immune microenvironment was performed on forty-seven clinically annotated olfactory neuroblastoma samples. A retrospective chart review was performed and clinical correlations assessed.
RESULTS: A significant T cell infiltration was noted in olfactory neuroblastoma samples with a stromal predilection, presence of myeloid-derived suppressor cells, and sparse natural killer cells. A striking decrease was observed in MHC-I expression in high-grade olfactory neuroblastoma compared to low-grade disease, representing a mechanism of immune evasion in high-grade disease. Mechanistically, the immune effector stromal predilection appears driven by low tumor cell MHC class II (HLA-DR), CXCL9, and CXCL10 expression as those tumors with increased tumor cell expression of each of these mediators correlated with significant increases in T cell infiltration.
CONCLUSIONS: These data suggest that immunotherapeutic strategies that augment tumor cell expression of MHC class II, CXCL9, and CXCL10 may improve parenchymal trafficking of immune effector cells in olfactory neuroblastoma and augment immunotherapeutic responses.
METHODS: Multispectral immunofluorescence and RNAScope evaluation of the tumor immune microenvironment was performed on forty-seven clinically annotated olfactory neuroblastoma samples. A retrospective chart review was performed and clinical correlations assessed.
RESULTS: A significant T cell infiltration was noted in olfactory neuroblastoma samples with a stromal predilection, presence of myeloid-derived suppressor cells, and sparse natural killer cells. A striking decrease was observed in MHC-I expression in high-grade olfactory neuroblastoma compared to low-grade disease, representing a mechanism of immune evasion in high-grade disease. Mechanistically, the immune effector stromal predilection appears driven by low tumor cell MHC class II (HLA-DR), CXCL9, and CXCL10 expression as those tumors with increased tumor cell expression of each of these mediators correlated with significant increases in T cell infiltration.
CONCLUSIONS: These data suggest that immunotherapeutic strategies that augment tumor cell expression of MHC class II, CXCL9, and CXCL10 may improve parenchymal trafficking of immune effector cells in olfactory neuroblastoma and augment immunotherapeutic responses.
摘要：
背景：嗅觉神经母细胞瘤是一种罕见的前颅底恶性肿瘤，通常采用手术和辅助放疗治疗。虽然结果对于低度疾病是公平的，高级患者，经常性,或转移性疾病通常对标准治疗方法反应不佳。我们假设对嗅觉神经母细胞瘤肿瘤免疫微环境的深入评估将确定高级嗅觉神经母细胞瘤的免疫逃避机制以及未来转化免疫治疗方法的合理靶向机制。
方法：对47个临床注释的嗅神经母细胞瘤样本进行了肿瘤免疫微环境的多光谱免疫荧光和RNAScope评估。进行回顾性图表回顾并评估临床相关性。
结果：在嗅觉神经母细胞瘤样本中发现明显的T细胞浸润，存在骨髓来源的抑制细胞，和稀疏的自然杀伤细胞。与低级别疾病相比，高级别嗅觉神经母细胞瘤中的MHC-I表达显着下降。代表了高级疾病中免疫逃避的机制。机械上,免疫效应基质好发出现由低肿瘤细胞MHCII类（HLA-DR）驱动，CXCL9和CXCL10表达作为具有这些介质中的每一种的肿瘤细胞表达增加的那些肿瘤与T细胞浸润的显著增加相关。
结论：这些数据表明，增强II类MHC肿瘤细胞表达的免疫治疗策略，CXCL9和CXCL10可以改善嗅神经母细胞瘤中免疫效应细胞的实质运输并增强免疫治疗反应。
方法：对47个临床注释的嗅神经母细胞瘤样本进行了肿瘤免疫微环境的多光谱免疫荧光和RNAScope评估。进行回顾性图表回顾并评估临床相关性。
结果：在嗅觉神经母细胞瘤样本中发现明显的T细胞浸润，存在骨髓来源的抑制细胞，和稀疏的自然杀伤细胞。与低级别疾病相比，高级别嗅觉神经母细胞瘤中的MHC-I表达显着下降。代表了高级疾病中免疫逃避的机制。机械上,免疫效应基质好发出现由低肿瘤细胞MHCII类（HLA-DR）驱动，CXCL9和CXCL10表达作为具有这些介质中的每一种的肿瘤细胞表达增加的那些肿瘤与T细胞浸润的显著增加相关。
结论：这些数据表明，增强II类MHC肿瘤细胞表达的免疫治疗策略，CXCL9和CXCL10可以改善嗅神经母细胞瘤中免疫效应细胞的实质运输并增强免疫治疗反应。
