肿瘤细胞治疗研究
英文原题：Immunoscore Signatures in Surgical Specimens and Tumor-Infiltrating Lymphocytes in Pretreatment Biopsy Predict Treatment Efficacy and Survival in Esophageal Cancer.
Immunoscore Signatures in Surgical Specimens and Tumor-Infiltrating Lymphocytes in Pretreatment Biopsy Predict Treatment Efficacy and Survival in Esophageal Cancer.
手术标本中的 IS 特征和 preNAC 活检中的 TIL 密度可能是食管癌（EC）患者临床结局的预测标志物。
目的：TIL（肿瘤浸润淋巴细胞）长期以来被认为在肿瘤免疫微环境中发挥重要作用。近期提出的免疫评分（IS）是一种新方法，用于定量TIL数量并分析其与多种癌症患者生存的关系。方法：纳入两家机构接受根治性切除、术前未治疗的300例食管癌（EC）患者，采用CD3和CD8抗体进行免疫组化染色；通过自动计数肿瘤核心区和浸润边缘的TIL，客观评估IS。此外，在另一组接受新辅助化疗（NAC）的146例EC患者中，对NAC前内镜活检样本进行CD3和CD8免疫染色，以评估TIL密度。结果：总体病例中，IS高组（评分3–4）的生存倾向于优于IS低组（评分1–2）[IS高组与低组5年总生存（OS）：77.6%比65.8%，P=0.0722]。在cStage II–IV患者中这一趋势更明显（70.2%比54.5%，P=0.0208）；OS多变量分析进一步显示IS是独立预后变量（风险比2.07，P=0.0043）。NAC前活检中，NAC应答者的CD3+细胞（P=0.0106）和CD8+细胞（P=0.0729）密度均高于非应答者；其中CD3+细胞密度被发现是独立预后因素（风险比1.75，P=0.0169）。结论：手术标本中的IS特征以及NAC前活检中的TIL密度，可能是EC患者临床结局的预测标志物。
OBJECTIVES: Tumor-infiltrating lymphocytes (TILs) have long been recognized as playing an important role in tumor immune microenvironment. Lately, the Immunoscore (IS) has been proposed as a new method of quantifying the number of TILs in association with patient survival in several cancer types. METHODS: In 300 preoperatively untreated esophageal cancer (EC) patients who underwent curative resection at two different institutes, immunohistochemical staining using CD3 and CD8 antibodies was performed to evaluate IS, as objectively scored by auto-counted TILs in the tumor core and invasive margin. In addition, in pre-neoadjuvant chemotherapy (pre-NAC) endoscopic biopsies of a different cohort of 146 EC patients who received NAC, CD3, and CD8 were immunostained to evaluate TIL density. RESULTS: In all cases, the IS-high (score 3-4) group tended to have better survival [5-year overall survival (OS) of the IS-high vs low group: 77.6 vs 65.8%, P = 0.0722] than the IS-low (score 1-2) group. This trend was more remarkable in cStage II-IV patients (70.2 vs 54.5%, P = 0.0208) and multivariate analysis of OS further identified IS (hazard ratio 2.07, P = 0.0043) to be an independent prognostic variable. In preNAC biopsies, NAC-responders had higher densities than non-responders of both CD3 + ( P = 0.0106) and CD8 + cells ( P = 0.0729) and, particularly CD3 + cell density was found to be an independent prognostic factor (hazard ratio 1.75, P = 0.0169). CONCLUSIONS: The IS signature in surgical specimens and TIL density in preNAC- biopsies could be predictive markers of clinical outcomes in EC patients.
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