BACKGROUND AND PURPOSE Tumour infiltrating lymphocytes (TIL) and tumour associated macrophages (TAM) play a key role in anticancer immunosurveillance. We studied their influence on response to neoadjuvant radiochemotherapy (RCT) and prognosis in patients with oesophageal adenocarcinoma (OAC). MATERIALS AND METHODS Between 10/2004 and 06/2018, pre-RCT biopsy-specimens were available from 76 patients with locally advanced, non-metastatic OAC scheduled for trimodality therapy. We evaluated intra- and peritumoural expression of FoxP3+-, CD8+-TIL and CD68+-, CD163+-TAM, contemplating cell density, cell ratios and cell-to-cell distances to determine a possible influence on tumour regression grade (TRG) and survival. Median follow-up time for all patients was 18 months (IQR 9-43), and 54 months (25-97) for surviving patients. Data were analysed using risk analysis, logrank test and Cox regression. RESULTS Poor tumour regression was detected for cN+ (RR 0.77 [95% CI 0.66-0.90], p = 0.001), low intratumoural FoxP3+/CD8+ ratio (RR 0.75 [0.60-0.96], p = 0.020), high peritumoural CD163+/CD68+ ratio (RR 0.77 [0.60-0.99], p = 0.045) and high intratumoural TAM density (RD -0.44 [-0.82 to -0.06], p = 0.023). Apart from poor resection quality and TRG, pretherapeutic high peritumoural CD8+ infiltration (HR 2.36 [1.21-4.61], p = 0.012) and short intratumoural FoxP3+ to CD8+ cell-to-cell distances in middle ranged CD8+ density (HR 2.55 [1.00-6.52], p = 0.050) were significant unfavourable prognostic factors in multivariate analysis. CONCLUSIONS Immunologic parameters, such as CD8+-, FoxP3+-TIL and CD68+-, CD163+-TAM, were identified to be of independent predictive and prognostic value in patients with OAC. Further and independent validation of these biomarkers by a large size dataset may urgently be contemplated.

中文翻译：

---

细胞毒性和免疫抑制性炎症细胞预测食管腺癌新辅助放化疗后的消退和预后

背景和目的 肿瘤浸润淋巴细胞 (TIL) 和肿瘤相关巨噬细胞 (TAM) 在抗癌免疫监视中起关键作用。我们研究了它们对食管腺癌 (OAC) 患者新辅助放化疗 (RCT) 反应和预后的影响。材料和方法 2004 年 10 月至 2018 年 6 月期间，从 76 名计划接受三联疗法的局部晚期非转移性 OAC 患者获得 RCT 前活检标本。我们评估了 FoxP3+-、CD8+-TIL 和 CD68+-、CD163+-TAM 的肿瘤内和肿瘤周围表达，考虑细胞密度、细胞比率和细胞间距离，以确定对肿瘤消退等级 (TRG) 和存活的可能影响。所有患者的中位随访时间为 18 个月 (IQR 9-43)，存活患者的中位随访时间为 54 个月 (25-97)。使用风险分析、对数秩检验和 Cox 回归分析数据。结果 检测到 cN+ 的肿瘤消退不佳（RR 0.77 [95% CI 0.66-0.90]，p = 0.001），瘤内 FoxP3+/CD8+ 比率低（RR 0.75 [0.60-0.96]，p = 0.020），高肿瘤周围 CD186/CD186比率（RR 0.77 [0.60-0.99]，p = 0.045）和高肿瘤内 TAM 密度（RD -0.44 [-0.82 至 -0.06]，p = 0.023）。除了较差的切除质量和 TRG 外，治疗前高肿瘤周围 CD8+ 浸润（HR 2.36 [1.21-4.61]，p = 0.012）和中等范围 CD85+ 密度的短瘤内 FoxP3+ 至 CD8+ 细胞间距离（HR 2.55 [1.00-6. ], p = 0.050) 在多变量分析中是显着的不利预后因素。结论免疫学参数，例如 CD8+-、FoxP3+-TIL 和 CD68+-、CD163+-TAM、被确定为对 OAC 患者具有独立的预测和预后价值。可能迫切需要考虑通过大型数据集对这些生物标志物进行进一步的独立验证。