机构规模的免疫谱分析表明，肿瘤内大量的CD8和PD-1细胞预示着主要癌症类型患者的生存情况更好，且不受主要风险因素的影响。
Immunoprofiling at an Institutional Scale Reveals That High Numbers of Intratumoral CD8 and PD-1 Cells Predict Superior Patient Survival Across Major Cancer Types Independent of Major Risk Factors.
作者信息
Alessi Joao V, Lindsay James R, Giobbie-Hurder Anita, Sharma Bijaya, Felt Kristen, Kumari Priti, Mazor Tali, Cerami Ethan, Lotter William, Altreuter Jennifer, Weirather Jason, Dryg Ian, Hoebel Katharina, Manos Michael, Adib Elio, Curtis Jennifer D, Ricciuti Biagio, Di Federico Alessandro, Ghandour Fatme, Saad Eddy, Wang Xin-An, Pecci Federica, Holovatska Marta, Gandhi Malini M, Hughes Melissa E, O'Meara Tess A, Chan Sabrina J, Pfaff Kathleen, Konstantinopoulos Panagiotis A, Hodi F Stephan, Shipp Margaret A, Signoretti Sabina, Choueiri Toni, Wei Xiao X, Santagata Sandro, Hanna Glenn J, Lin Nancy U, Tolaney Sara M, Liu Joyce, Sorger Peter K, Lindeman Neal, Sholl Lynette M, Nowak Jonathan A, Barbie David, Awad Mark M, Johnson Bruce E, Rodig Scott J
机构信息
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
Department of Data Science, Dana-Farber Cancer Institute, Boston, MA.
出版信息
JCO Precis Oncol. 2025 Sep;9:e2500240. doi: 10.1200/PO-25-00240. Epub 2025 Sep 4.
PURPOSE
Retrospective studies have found associations between the number of intratumoral immune cells and patient outcomes for specific cancers treated with targeted therapies. However, the clinical value of routinely quantifying intratumoral immune biomarkers using a digital pathology platform in the pan-cancer setting within an active clinical laboratory has not been established.
METHODS
We developed ImmunoProfile, a daily clinical workflow that integrates automated multiplex immunofluorescence tissue staining, digital slide imaging, and machine learning-assisted scoring to quantify intratumoral CD8, PD-1, CD8PD-1, and FOXP3 immune cells and PD-L1 expression in formalin-fixed, paraffin-embedded tissue samples in a standardized and reproducible manner. We prospectively applied ImmunoProfile to biopsies collected from 2,023 unselected patients with cancer over a 3-year period in the clinical laboratory and correlated the results with patient survival.
RESULTS
In the pan-cancer cohort, patients with high numbers of intratumoral CD8 or PD-1 cells in had significantly lower risks of death compared with those with low numbers (CD8: high low hazard ratio [HR], 0.62 [95% CI, 0.48 to 0.81], Wald = .002; PD-1: high low HR, 0.65 [95% CI, 0.51 to 0.83]; = .0009) after adjusting for risk factors, including cancer type. In subset analyses, patients with high numbers of intratumoral CD8, PD-1, and/or CD8PD-1 cells showed lower risks of death from non-small cell lung, colorectal, breast, esophagogastric, head and neck, pancreatic, and ovarian cancers after considering clinical risk factors, including American Joint Committee on Cancer stage, and despite varying therapies (all < .05).
CONCLUSION
Routinely quantifying intratumoral CD8 and PD-1 cells with a clinically validated digital pathology platform predicts patient survival across major cancer types, independent of clinical stage and despite diverse treatment regimens.
目的
回顾性研究发现，肿瘤内免疫细胞数量与接受靶向治疗的特定癌症患者的预后之间存在关联。然而，在活跃的临床实验室中，使用数字病理平台在泛癌环境中常规量化肿瘤内免疫生物标志物的临床价值尚未确立。
方法
我们开发了免疫图谱（ImmunoProfile），这是一种日常临床工作流程，整合了自动多重免疫荧光组织染色、数字载玻片成像和机器学习辅助评分，以标准化和可重复的方式量化福尔马林固定、石蜡包埋组织样本中的肿瘤内CD8、PD-1、CD8⁺PD-1和FOXP3免疫细胞以及PD-L1表达。我们前瞻性地将免疫图谱应用于临床实验室在3年期间从2023例未经选择的癌症患者中采集的活检样本，并将结果与患者生存率相关联。
结果
在泛癌队列中，与肿瘤内CD8或PD-1细胞数量低的患者相比，数量高的患者在调整包括癌症类型在内的风险因素后，死亡风险显著更低（CD8：高 vs 低风险比[HR]，0.62[95%CI，0.48至0.81]，Wald检验P = 0.002；PD-1：高 vs 低HR，0.65[95%CI，0.51至0.83]；P = 0.0009）。在亚组分析中，在考虑包括美国癌症联合委员会分期在内的临床风险因素后，尽管治疗方法不同，但肿瘤内CD8、PD-1和/或CD8⁺PD-1细胞数量高的患者死于非小细胞肺癌、结直肠癌、乳腺癌、食管胃癌、头颈癌、胰腺癌和卵巢癌的风险更低（所有P < 0.05）。
结论
使用经过临床验证的数字病理平台常规量化肿瘤内CD8和PD-1细胞可预测主要癌症类型患者的生存情况，独立于临床分期且尽管治疗方案多样。
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