CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Prognostic Value of Tumor-Infiltrating Lymphocytes in Resected Pancreatic Ductal Adenocarcinoma: A Single-Center Retrospective Australian Study.
Prognostic Value of Tumor-Infiltrating Lymphocytes in Resected Pancreatic Ductal Adenocarcinoma: A Single-Center Retrospective Australian Study.
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**引言：**即使接受根治意图切除，胰腺导管腺癌（PDAC）预后仍较差。免疫组化评估的TIL（肿瘤浸润淋巴细胞）具有预后价值，但常规H&E切片的标准化评估尚未确立，澳大利亚队列尤然。本试点研究依据国际免疫肿瘤生物标志物工作组（ITWG）指南，在切除PDAC的H&E切片上评估基质TIL密度，并探索其与生存和关键临床病理指标的关系。**方法：**回顾性队列纳入2016年9月至2025年1月在澳大利亚一家三级中心接受根治意图切除、组织学确诊PDAC的连续21例患者。在H&E切片上定量基质TIL，并预先分为低浸润（<15%）和高浸润（≥15%）。采用Kaplan-Meier法和log-rank检验分析总生存期（OS）和无病生存期（DFS）。先进行单变量Cox回归，再建立探索性多变量Cox模型，纳入基质TIL类别、淋巴结比率（LNR）和血管侵犯。**结果：**中位随访17个月（范围3–99个月），11例死亡（52%），12例复发（57%）。
按预设15%基质TIL阈值，10例为低TIL，11例为高TIL。与低TIL相比，高TIL与OS改善相关（中位数未达到比16个月；log-rank P=0.029），DFS也改善（中位数未达到比9个月；P=0.026）。探索性多变量模型中，高TIL仍与OS改善（HR=0.15，P=0.033）及DFS改善（HR=0.18，P=0.024）相关。LNR较高与OS较差（每增加10% HR=3.42，P=0.005）及DFS较差（每增加10% HR=2.41，P=0.010）相关。将TIL作为连续变量（每增加5%）分析时，效应方向一致，但OS（HR=0.94，P=0.155）和DFS（HR=0.94，P=0.115）均未达到统计学显著性。**结论：**在这项澳大利亚单中心试点队列中，常规H&E切片评估的基质TIL较高与PDAC切除后OS和DFS改善相关。结果支持依据ITWG指南评估基质TIL的可行性和潜在预后价值，并有必要在更大规模多中心研究中验证。
Introduction Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, even after curative-intent resection. Tumor-infiltrating lymphocytes (TILs) assessed by immunohistochemistry have prognostic value, but standardized assessment on routine H&E sections is not established, particularly in Australian cohorts. This pilot study evaluated stromal TIL density in resected PDAC on H&E sections using the International Immuno-Oncology Biomarker Working Group (ITWG) guidelines and explored its association with survival and key clinicopathological metrics.
Methods We conducted a retrospective cohort study of 21 consecutive patients who underwent curative-intent resection for histologically confirmed PDAC at an Australian tertiary center between September 2016 and January 2025. Stromal TIL density was quantified on H&E sections and categorized a priori as low (<15%) or high ( 15%) lymphocytic infiltration of the tumor stroma.
Overall survival (OS) and disease-free survival (DFS) were analyzed using Kaplan-Meier methods and log-rank tests. Univariable Cox regression was performed, followed by an exploratory multivariable Cox model incorporating stromal TIL category, lymph node ratio (LNR), and vascular invasion. Results Median follow-up was 17 months (range, 3-99), with 11 deaths (52%) and 12 recurrences (57%). Using the prespecified threshold of 15% stromal TIL density, 10 patients had low stromal TILs, and 11 had high stromal TILs. Compared with low TILs, high TILs were associated with improved OS (median not reached vs. 16 months; log-rank p = 0. 029) and DFS (median not reached vs. nine months; log-rank p = 0.
026). In the exploratory multivariable model, high TILs remained associated with improved OS (HR 0. 15, p = 0. 033) and DFS (HR 0. 18, p = 0. 024). A higher LNR was associated with poorer OS (HR 3. 42 per 10% increase, p = 0. 005) and DFS (HR 2. 41 per 10% increase, p = 0. 010).
When analyzed as a continuous variable (per 5% increase), stromal TIL density showed a consistent direction of effect without statistical significance for OS (HR 0. 94, p = 0. 155) or DFS (HR 0. 94, p = 0. 115). Conclusions In this single-center Australian pilot cohort, high stromal TIL density assessed on routine H&E sections was associated with improved OS and DFS following PDAC resection.
These findings support the feasibility and potential prognostic utility of stromal TIL assessment using ITWG guidelines and warrant validation in larger multicenter studies.
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