Yang Yunyun, Wan Zhiyi, Zhang Enli, Piao Yingshi
Department of Pathology, Beijing Tongren Hospital Affiliated to Capital Medical University, Beijing, China.
Department of Medicine, Beijing Key Laboratory of Head and Neck Molecular Diagnostic Pathology, Beijing, China.
Front Oncol. 2023 Nov 1;13:1226494. doi: 10.3389/fonc.2023.1226494. eCollection 2023.
Olfactory neuroblastoma (ONB) is a rare malignant neoplasm of the olfactory mucosa. The paucity of genomic data has prevented the development of individualized ONB treatments. Here, we investigated the genomic and immune landscape of ONB in Chinese patients.
Whole exome sequencing (WES) and multiplex immunofluorescence (MIF) analysis were performed on tissue samples from 19 Chinese ONB patients. Patients were divided into low- and high-grade groups.
Overall, 929 nonsynonymous alterations were identified in 18 (94.74%) ONB cases. The most prevalent altered cancer-related genes were (16%) and (16%). The most mutated oncogenic pathways were the WNT and RAS pathways. The median tumor mutation burden (TMB) was 0.45, ranging from 0 to 3.25. Only one case expressed PD-L1 (> 1%) in the tumor region. The percentage of CD8+ tumor-infiltrating lymphocytes (TILs) in the tumor region ranged from 0.03% to 84.9%, with a median of 1.08%. No significant differences were observed between the low- and high-grade groups for clinicopathological features, mutant genes, mutant pathways, TMB, tumor neoantigen burden (TNB), mutant-allele tumor heterogeneity (MATH), PD-L1 expression levels, or CD8+ TIL percentage. However, the low-grade group showed significantly more CD68+ macrophages in both the tumor and total region than the high-grade group. Notably, CD68+CD163- macrophages accounted for an average of 80.5% of CD68+ macrophages.
This study presents data on the genomic and immune landscape of ONB cases in China. and were the most prevalent altered cancer-related genes. The results of TMB, PD-L1, and CD8+ Tils suggest that ONB may be insensitive to immunotherapy. M1 macrophages may be positively associated with the prognosis of ONB.
In this study, the most prevalent altered cancer-related genes were (16%) and (16%). The most mutated oncogenic pathways were the WNT and RAS pathways. The median tumor mutation burden (TMB) was 0.45, ranging from 0 to 3.25. Only one (1/15) case expressed PD-L1 (> 1%) in the tumor region. However, the low-grade group showed significantly more CD68+ macrophages in both the tumor and total region than the high-grade group. The higher level of CD68-related macrophages indicates that M1 macrophages potentially play an important role in ONB development that is possibly associated with prognosis.
嗅神经母细胞瘤（ONB）是一种罕见的嗅黏膜恶性肿瘤。基因组数据的匮乏阻碍了ONB个体化治疗的发展。在此，我们研究了中国患者ONB的基因组和免疫图谱。
对19例中国ONB患者的组织样本进行全外显子组测序（WES）和多重免疫荧光（MIF）分析。患者被分为低级别和高级别组。
总体而言，在18例（94.74%）ONB病例中鉴定出929个非同义改变。最常见的与癌症相关的改变基因是（16%）和（16%）。最常发生突变的致癌途径是WNT和RAS途径。肿瘤突变负荷（TMB）中位数为0.45，范围为0至3.25。肿瘤区域仅1例表达PD-L1（>1%）。肿瘤区域CD8+肿瘤浸润淋巴细胞（TILs）百分比范围为0.03%至84.9%，中位数为1.08%。低级别和高级别组在临床病理特征、突变基因、突变途径、TMB、肿瘤新抗原负荷（TNB）、突变等位基因肿瘤异质性（MATH）、PD-L1表达水平或CD8+TIL百分比方面未观察到显著差异。然而，低级别组在肿瘤和整体区域的CD68+巨噬细胞均显著多于高级别组。值得注意的是，CD68+CD163-巨噬细胞平均占CD68+巨噬细胞的80.5%。
本研究展示了中国ONB病例的基因组和免疫图谱数据。和是最常见的与癌症相关的改变基因。TMB、PD-L1和CD8+TILs的结果表明ONB可能对免疫治疗不敏感。M1巨噬细胞可能与ONB的预后呈正相关。
在本研究中，最常见的与癌症相关的改变基因是（16%）和（16%）。最常发生突变的致癌途径是WNT和RAS途径。肿瘤突变负荷（TMB）中位数为0.45，范围为0至3.25。肿瘤区域仅1例（1/15）表达PD-L1（>1%）。然而，低级别组在肿瘤和整体区域的CD68+巨噬细胞均显著多于高级别组。CD68相关巨噬细胞水平较高表明M1巨噬细胞可能在ONB发展中起重要作用，可能与预后相关。
