Table_1_High immune cell infiltration predicts improved survival in cholangiocarcinoma.docx

BackgroundAntitumoral immune response has a crucial role in constraining cancer. However, previous studies on cholangiocarcinoma (CCA), a rare and aggressive cancer, have reported contradictory findings on the prognostic impact of tumor-infiltrating T-lymphocytes. We aimed to clarify the effect of tumor-infiltrating CD3+ and CD8+ lymphocytes and PD-1/PD-L1 expression on CCA prognosis.
MethodsCD3+, CD8+, and PD-1+ lymphocyte densities, as well as PD-L1 expression rate were analyzed from stained tissue microarray samples from the tumor center and invasive margin of 47 cholangiocarcinomas. The association of CD3+ and CD8+ based Immune cell score (ICS) and its components with overall survival was evaluated, adjusting for age, sex, TNM stage, radicality of surgery, tumor location, and PD-L1 expression on immune cells.
ResultsLow ICS was a strong independent prognostic factor for worse overall survival (Hazard ratio 9.27, 95% confidence interval 2.72-31.64, P<0.001). Among the ICS components, high CD8+ lymphocyte infiltration at the tumor center had the most evident impact on patient outcome. PD-1 and PD-L1 expression on immune cells did not have a significant impact on overall survival alone; however, PD-L1 positivity seemed to impair survival for ICSlow subgroup.
ConclusionIdentifying patient subgroups that could benefit from immunotherapy with PD-1/PD-L1 pathway blockade may help improve treatment strategies for this aggressive cancer. Our findings highlight the importance of evaluating the immune contexture in cholangiocarcinoma, as ICS serves as a strong independent prognostic and selective factor for patients who might benefit from immunotherapy.

背景
抗肿瘤免疫应答在抑制肿瘤发生发展中发挥关键作用。然而，针对胆管癌（cholangiocarcinoma, CCA）——一种罕见且侵袭性极强的恶性肿瘤——既往相关研究中，关于肿瘤浸润性T淋巴细胞的预后影响报道存在矛盾。本研究旨在明确肿瘤浸润性CD3+、CD8+淋巴细胞以及PD-1/PD-L1表达对胆管癌预后的影响。

方法
本研究对47例胆管癌患者的肿瘤中心及侵袭边缘的染色组织微阵列样本进行分析，检测CD3+、CD8+、PD-1+淋巴细胞密度以及PD-L1表达率。本研究评估了基于CD3+与CD8+淋巴细胞的免疫细胞评分（immune cell score, ICS）及其组成成分与总生存期的关联，并校正了年龄、性别、TNM分期、手术根治性、肿瘤部位及免疫细胞PD-L1表达等混杂因素。

结果
低免疫细胞评分是总生存期较差的强独立预后因素（风险比9.27，95%置信区间2.72~31.64，P<0.001）。在免疫细胞评分的组成成分中，肿瘤中心区域的高CD8+淋巴细胞浸润对患者预后的影响最为显著。免疫细胞上的PD-1与PD-L1单独表达并未对总生存期产生显著影响；然而，PD-L1阳性似乎会缩短免疫细胞评分低亚组患者的生存期。

结论
识别可从PD-1/PD-L1通路阻断免疫治疗中获益的患者亚组，有助于优化这类侵袭性恶性肿瘤的治疗策略。本研究结果凸显了评估胆管癌免疫浸润格局的重要性，免疫细胞评分可作为强独立预后因子，同时也是筛选可能从免疫治疗中获益患者的有效指标。