CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Genomic profiling and immune landscape of olfactory neuroblastoma in China.
Genomic profiling and immune landscape of olfactory neuroblastoma in China.
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本研究呈现了中国 ONB 病例的基因组和免疫景观数据。
嗅神经母细胞瘤（ONB）是一种起源于嗅黏膜的罕见恶性肿瘤。基因组数据匮乏阻碍了个体化ONB治疗的开发。本研究考察了中国患者ONB的基因组特征和免疫图谱。
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，并将患者分为低级别和高级别组。
18例（94.74%）ONB病例共发现929个非同义改变。最常见的癌症相关基因改变为CTNNB1（16%）和ZNRF3（16%）；突变最多的致癌通路为WNT和RAS通路。肿瘤突变负荷（TMB）中位数为0.45，范围0–3.25。仅1例肿瘤区域PD-L1表达超过1%。肿瘤区域CD8+TIL（肿瘤浸润淋巴细胞）比例为0.03%–84.9%，中位数为1.08%。低级别与高级别组在临床病理特征、突变基因、突变通路、TMB、肿瘤新抗原负荷（TNB）、突变等位基因肿瘤异质性（MATH）、PD-L1表达水平及CD8+ TIL比例方面均无显著差异。然而，低级别组肿瘤区和全区域的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%。
本研究报告了中国ONB病例的基因组特征和免疫图谱。CTNNB1和ZNRF3是最常见的改变基因。TMB、PD-L1和CD8+ TIL结果提示，ONB可能对免疫治疗不敏感。M1型巨噬细胞可能与ONB预后较好正相关。实践意义：本研究中最常见的癌症相关基因改变是CTNNB1（16%）和ZNRF3（16%），突变最多的致癌通路为WNT和RAS通路。TMB中位数为0.45，范围0–3.25。肿瘤区域仅1/15例PD-L1表达超过1%。但低级别组肿瘤及全区域的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提示，M1型巨噬细胞可能在ONB进展中发挥重要作用，并可能与预后相关。
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 CTNNB1 (16%) and ZNRF3 (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. CTNNB1 and ZNRF3 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. IMPLICATIONS FOR PRACTICE: In this study, the most prevalent altered cancer-related genes were CTNNB1 (16%) and ZNRF3 (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.
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