肿瘤细胞治疗研究
英文原题：Exploratory evaluation of the somatic and immunologic landscape of primary and metastatic cervical cancer to better inform future clinical trial development.
Exploratory evaluation of the somatic and immunologic landscape of primary and metastatic cervical cancer to better inform future clinical trial development.
原发灶和转移灶的分子和免疫分析表明，肝脏病灶具有较低的免疫原性微环境。
目的：探究宫颈癌原发灶与转移灶的体细胞和免疫特征，以评估不同宫颈癌转移部位对治疗的敏感性差异及潜在治疗意义。 方法：研究从Tempus数据库（2016–2023年）选取接受测序的宫颈鳞癌患者，纳入136份非配对样本（原发灶73份、转移灶63份）。评估致病性体细胞突变及免疫细胞基因表达模式，并比较不同肿瘤部位的免疫细胞比例、肿瘤突变负荷和肿瘤新抗原负荷。采用χ²/Fisher确切检验或Kruskal–Wallis检验评估统计学显著性。 结果：队列中位年龄为52岁（四分位距42–60岁）。9.6%的患者存在高肿瘤突变负荷（≥10个突变/Mb；原发灶9%、肺转移0%、肝转移17%、淋巴结转移17%，P=.7）。1.5%的患者存在高微卫星不稳定性（MSI，P=.7）。78%的患者PD-L1阳性（原发灶76%、肺转移88%、肝转移71%、淋巴结转移80%，P=.8）。肿瘤新抗原负荷中位数为1.71（四分位距0.98–3.20）。与其他部位相比，肝转移灶B细胞比例最低（P=.001），巨噬细胞比例较高（P=.053）。与其他部位相比，淋巴结转移灶CD4细胞比例（P=.053）和NK细胞比例（P=.090）有较低趋势。PIK3CA是最常见的致病性体细胞改变，但不同部位间无统计学差异（q=.9）。 结论：对原发灶和转移灶进行分子及免疫谱分析表明，肝转移灶的微环境免疫原性较低。仍需进一步分析配对样本中的分子图谱，以更好地指导新疗法的开发和应用。
OBJECTIVE: To explore the somatic and immunologic landscape of cervical primary versus metastatic tumors for differential sensitivity of metastatic cervical sites and potential therapeutic implications. METHODS: Patients with sequenced squamous cell cervical cancer were selected from the Tempus Database (2016-2023). The cohort included 136 unmatched samples (73 primary, 63 metastatic sites). Pathogenic somatic mutations and gene expression patterns of immune cells were evaluated for relative intratumor abundance. Immune cell percentages, tumor mutational burden, and tumor neoantigen burden (tumor mutational burden) were compared across tumor sites. χ 2 /Fisher exact tests or Kruskal-Wallis tests were used to assess statistical significance. RESULTS: The median cohort age was 52 years (interquartile range; 42-60). High tumor mutational burden (≥ 10 mut/Mb) was seen in 9.6% (9% primary, 0% lung, 17% liver, 17% lymph node, p = .7) of patients. High microsatellite instability (MSI) was noted in 1.5% (p = .7) of patients. PD-L1 status was positive in 78% (76% primary, 88% lung, 71% liver, and 80% lymph node, p = .8) of patients. Median tumor neoantigen burden was 1.71 (interquartile range; 0.98-3.20). Liver lesions had the lowest percentage of B cells (p = .001) and a higher percentage of macrophages (p = .053) compared with other sites. There was a trend toward lower percentages of CD4 cells (p = .053) and natural killer cells (p = .090) in lymph nodes compared with other sites. PIK3CA was the most common pathogenic somatic alteration but not statistically different across sites (q = 0.9). CONCLUSIONS: Molecular and immune profiling of primary and metastatic lesions indicated that liver lesions had a less immunogenic microenvironment. Further interrogation of the molecular landscape across paired samples is needed to better inform the development and use of novel therapies.
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