Stratification of chemotherapy-treated stage III colorectal cancer patients using multiplexed imaging and single-cell analysis of T-cell populations.
Stratification of chemotherapy-treated stage III colorectal cancer patients using multiplexed imaging and single-cell analysis of T-cell populations.
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DOI：
10.1038/s41379-021-00953-0
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发表时间：
2022-04
期刊：
影响因子：
--
通讯作者：
Longley DB
中科院分区：
文献类型：
--
作者：
Stachtea X;Loughrey MB;Salvucci M;Lindner AU;Cho S;McDonough E;Sood A;Graf J;Santamaria-Pang A;Corwin A;Laurent-Puig P;Dasgupta S;Shia J;Owens JR;Abate S;Van Schaeybroeck S;Lawler M;Prehn JHM;Ginty F;Longley DB
结直肠癌（CRC）是发病率和死亡率最高的癌症之一。在III期，术后化疗获益的患者<20%，而超过50%的患者会发生远处转移。目前缺乏用于识别辅助化疗后疾病复发风险增加的患者的生物标志物。在这项研究中，我们使用原位多重免疫荧光成像和单细胞分析技术 (Cell DIVETM) 评估了肿瘤和肿瘤微环境 (TME) 中的免疫特征，并评估了它们与患者结果的相关性。从 117 名接受氟嘧啶/奥沙利铂 (FOLFOX) 辅助化疗的 III 期 CRC 患者中制备每个患者最多三个 1mm 直径核心的组织微阵列 (TMA)。单切片对免疫细胞标记物（CD45、CD3、CD4、CD8、FOXP3、PD1）和肿瘤/细胞分割标记物（DAPI、泛细胞角蛋白、AE1、NaKATPase 和 S6）进行多重免疫荧光染色。我们使用注释和概率分类算法来构建免疫细胞类型的统计模型。病理学家还对图像的基质和总免疫细胞含量独立定性评估为“高”、“中”或“低”。手动评估和自动总得分之间存在极好的一致性 (p< 0.0001)。此外，与单一标志物相比，调节性T细胞（Treg：CD3+/CD4+FOXP3+/PD1-）的多标志物分类与FOLFOX治疗患者的无病生存（DFS）和总生存（OS）显着相关（p = 0.049和0.032）。我们的结果还表明，PD1− Tregs 而非 PD1+ Tregs 与生存率提高相关。这些发现得到了由 191 名 III 期 CRC 患者组成的独立 FOLFOX 治疗队列的结果的支持，其中较高的 PD1− Tregs 与 CD3+/CD4+/FOXP3+/PD1− 的总生存期增加相关 (p = 0.015)。总体而言，与单一标记物相比，多标记物分类可提供更准确的免疫细胞类型定量，且与结果的相关性更强。
Colorectal cancer (CRC) has one of the highest cancer incidences and mortality rates. In stage III, postoperative chemotherapy benefits <20% of patients, while more than 50% will develop distant metastases. Biomarkers for identification of patients at increased risk of disease recurrence following adjuvant chemotherapy are currently lacking. In this study, we assessed immune signatures in the tumor and tumor microenvironment (TME) using an in situ multiplexed immunofluorescence imaging and single-cell analysis technology (Cell DIVETM) and evaluated their correlations with patient outcomes. Tissue microarrays (TMAs) with up to three 1 mm diameter cores per patient were prepared from 117 stage III CRC patients treated with adjuvant fluoropyrimidine/oxaliplatin (FOLFOX) chemotherapy. Single sections underwent multiplexed immunofluorescence staining for immune cell markers (CD45, CD3, CD4, CD8, FOXP3, PD1) and tumor/cell segmentation markers (DAPI, pan-cytokeratin, AE1, NaKATPase, and S6). We used annotations and a probabilistic classification algorithm to build statistical models of immune cell types. Images were also qualitatively assessed independently by a Pathologist as ‘high’, ‘moderate’ or ‘low’, for stromal and total immune cell content. Excellent agreement was found between manual assessment and total automated scores (p < 0.0001). Moreover, compared to single markers, a multi-marker classification of regulatory T cells (Tregs: CD3+/CD4+FOXP3+/PD1−) was significantly associated with disease-free survival (DFS) and overall survival (OS) (p = 0.049 and 0.032) of FOLFOX-treated patients. Our results also showed that PD1− Tregs rather than PD1+ Tregs were associated with improved survival. These findings were supported by results from an independent FOLFOX-treated cohort of 191 stage III CRC patients, where higher PD1− Tregs were associated with an increase overall survival (p = 0.015) for CD3+/CD4+/FOXP3+/PD1−. Overall, compared to single markers, multi-marker classification provided more accurate quantitation of immune cell types with stronger correlations with outcomes.
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影响因子：
--
作者：
Elkord E;Abd Al Samid M;Chaudhary B
通讯作者：
Chaudhary B
影响因子：
4.6
作者：
Allen WL;Dunne PD;McDade S;Scanlon E;Loughrey M;Coleman H;McCann C;McLaughlin K;Nemeth Z;Syed N;Jithesh P;Arthur K;Wilson R;Coyle V;McArt D;Murray GI;Samuel L;Nuciforo P;Jimenez J;Argiles G;Dienstmann R;Tabernero J;Messerini L;Nobili S;Mini E;Sheahan K;Ryan E;Johnston PG;Van Schaeybroeck S;Lawler M;Longley DB
通讯作者：
Longley DB
影响因子：
64.5
作者：
Goltsev Y;Samusik N;Kennedy-Darling J;Bhate S;Hale M;Vazquez G;Black S;Nolan GP
通讯作者：
Nolan GP
影响因子：
--
作者：
Hu G;Li Z;Wang S
通讯作者：
Wang S
DOI：
10.1097/cji.0b013e3181d32f01
发表时间：
2010-05
期刊：
Journal of immunotherapy (Hagerstown, Md. : 1997)
影响因子：
--
作者：
Correale P;Rotundo MS;Del Vecchio MT;Remondo C;Migali C;Ginanneschi C;Tsang KY;Licchetta A;Mannucci S;Loiacono L;Tassone P;Francini G;Tagliaferri P
通讯作者：
Tagliaferri P