喉癌发生过程中免疫微环境的空间重塑揭示喉鳞状细胞癌的预后免疫模式
Spatial Remodeling of the Immune Microenvironment During Laryngeal Carcinogenesis Reveals Prognostic Immune Patterns in Laryngeal Squamous Cell Carcinoma.
文献信息
| PMID | 42882825 |
|---|---|
| 原文 | 在 PubMed 查看原文 ↗ |
| 发表日期 | 2026 |
| 作者 | Toni Vidović |
| 作者单位 | Department of Otorhinolaryngology, Head and Neck Surgery, Clinical Hospital Center Rijeka, 51000 Rijeka, Croatia. |
| 期刊 | Cancers |
| SCI 分区 | Q2 |
| IF | 5.1 |
| 研究类型 | 临床研究 · 临床 |
| 所属专科 | 咽喉科 |
中文摘要
背景/目的： 尽管治疗取得进展，喉鳞状细胞癌（LSCC）仍是临床挑战。我们研究了喉癌发生过程中免疫微环境的重塑及其预后相关性。
方法： 这项回顾性研究纳入227例患者：45例良性喉息肉、55例喉上皮异型增生和127例LSCC；55例（43.3%）LSCC为国际抗癌联盟（UICC）I-II期，72例（56.7%）为III-IV期。采用组织微阵列（TMA）免疫组织化学评估分化簇（CD）4、CD8、叉头框P3（FOXP3）、程序性细胞死亡蛋白1（PD-1）、细胞毒性T淋巴细胞相关蛋白4（CTLA-4）、CD68和CD163阳性免疫细胞以及FOXP3/CTLA-4双阳性细胞的密度。免疫细胞密度以阳性染色免疫细胞占相应上皮内/瘤内或间质区室的百分比表示。探索性保护性免疫评分（PIS；0-2）对上皮内FOXP3高密度和间质CTLA-4高密度各赋1分。
结果： LSCC显示间质免疫细胞密度增加和协调的免疫组织化。间质PD-1与CD4、CD8和FOXP3密度相关（rs = 0.561、0.515和0.403），间质CTLA-4与FOXP3相关（rs = 0.556；均p < 0.0001）。上皮内FOXP3高密度与疾病特异性生存（DSS；风险比[HR] = 0.26，95%置信区间[CI] 0.10-0.72）和无病生存（DFS；HR = 0.24，95% CI 0.10-0.59）改善相关。间质CTLA-4高密度同样有利于DSS（HR = 0.29，95% CI 0.11-0.74）和DFS（HR = 0.26，95% CI 0.11-0.61）。PIS仍与DSS（校正HR = 0.29，95% CI 0.16-0.55）和DFS（校正HR = 0.29，95% CI 0.17-0.52）独立相关。
结论： 喉癌发生的特征是进行性、区室特异性的免疫重塑，间质成为协调免疫组织化的主要部位。PIS捕捉了空间定义的有利免疫特征，值得在独立队列中验证。
英文摘要
BACKGROUND/OBJECTIVES: Despite therapeutic advances, laryngeal squamous cell carcinoma (LSCC) remains a clinical challenge. We investigated immune microenvironment remodeling and its prognostic relevance during laryngeal carcinogenesis.
METHODS: This retrospective study included 227 patients: 45 with benign laryngeal polyps, 55 with laryngeal epithelial dysplasia, and 127 with LSCC; 55 (43.3%) LSCCs were Union for International Cancer Control (UICC) stage I-II and 72 (56.7%) stage III-IV. Immunohistochemistry on tissue microarrays (TMAs) was used to assess the density of cluster of differentiation (CD)4-, CD8-, forkhead box P3 (FOXP3)-, programmed cell death protein 1 (PD-1)-, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)-, CD68-, and CD163-positive immune cells, together with FOXP3/CTLA-4 double-positive cells. Immune-cell densities were expressed as the percentage of the respective intraepithelial/intratumoral or stromal compartment occupied by positively stained immune cells. An exploratory Protective Immune Score (PIS; 0-2) assigned one point each for high intraepithelial FOXP3 and high stromal CTLA-4 cell density.
RESULTS: LSCC showed increased stromal immune-cell density and coordinated immune organization. Stromal PD-1 correlated with CD4, CD8, and FOXP3 density (rs = 0.561, 0.515, and 0.403), and stromal CTLA-4 with FOXP3 (rs = 0.556; all p < 0.0001). High intraepithelial FOXP3 was associated with improved disease-specific survival (DSS; hazard ratio [HR] = 0.26, 95% confidence interval [CI] 0.10-0.72) and disease-free survival (DFS; HR = 0.24, 95% CI 0.10-0.59). High stromal CTLA-4 similarly favored DSS (HR = 0.29, 95% CI 0.11-0.74) and DFS (HR = 0.26, 95% CI 0.11-0.61). The PIS remained independently associated with DSS (adjusted HR = 0.29, 95% CI 0.16-0.55) and DFS (adjusted HR = 0.29, 95% CI 0.17-0.52).
CONCLUSIONS: Laryngeal carcinogenesis is characterized by progressive, compartment-specific immune remodeling, with the stroma emerging as the principal site of coordinated immune organization. The PIS captures spatially defined favorable immune features and warrants validation in independent cohorts.