Highly Multiplexed Phenotyping of Immunoregulatory Proteins in the Tumor Microenvironment by CODEX Tissue Imaging.
Highly Multiplexed Phenotyping of Immunoregulatory Proteins in the Tumor Microenvironment by CODEX Tissue Imaging.
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DOI：
10.3389/fimmu.2021.687673
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发表时间：
2021
影响因子：
7.3
通讯作者：
Jiang S
中科院分区：
文献类型：
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作者：
Phillips D;Schürch CM;Khodadoust MS;Kim YH;Nolan GP;Jiang S
免疫疗法通过增强免疫系统的自然能力来彻底改变癌症治疗。除了针对传统检查点分子或其配体（即，在一些实施方案中，靶向分子（如CTLA-4、PD-1和PD-L1）的疗法目前处于临床试验中，靶向分子如ICOS、IDO-1、LAG-3、OX 40、TIM-3和VISTA的疗法目前处于临床试验中。为了更好地告知临床护理和治疗组合策略的设计，必须稳健地表征肿瘤微环境内单个免疫细胞上的免疫调节蛋白的共表达。高度多路复用的组织成像平台，如CO-Detection by indEXing（CODEX），通过在福尔马林固定的石蜡包埋（FFPE）组织切片上的单细胞中同时分析>50种标记物来满足这一需求。就抗原检测的特异性和背景信号的稳健性而言，抗体组的组装和验证尤其具有挑战性。在这里，我们报告的设计，开发，优化和应用的56标记CODEX抗体面板8皮肤T细胞淋巴瘤（CTCL）患者样本。该小组由结构，肿瘤和免疫细胞标志物组成，包括八种已被批准或目前正在进行临床试验的免疫调节蛋白作为免疫治疗靶点。在这里，我们提供了一个资源，使广泛的高维，空间分辨表征的组织微环境跨肿瘤类型和成像模式。该框架为研究人员提供了一个易于应用的蓝图，以研究肿瘤免疫学，组织结构，并实现对免疫靶点的机制见解。
Immunotherapies are revolutionizing cancer treatment by boosting the natural ability of the immune system. In addition to antibodies against traditional checkpoint molecules or their ligands (i.e., CTLA-4, PD-1, and PD-L1), therapies targeting molecules such as ICOS, IDO-1, LAG-3, OX40, TIM-3, and VISTA are currently in clinical trials. To better inform clinical care and the design of therapeutic combination strategies, the co-expression of immunoregulatory proteins on individual immune cells within the tumor microenvironment must be robustly characterized. Highly multiplexed tissue imaging platforms, such as CO-Detection by indEXing (CODEX), are primed to meet this need by enabling >50 markers to be simultaneously analyzed in single-cells on formalin-fixed paraffin-embedded (FFPE) tissue sections. Assembly and validation of antibody panels is particularly challenging, with respect to the specificity of antigen detection and robustness of signal over background. Herein, we report the design, development, optimization, and application of a 56-marker CODEX antibody panel to eight cutaneous T cell lymphoma (CTCL) patient samples. This panel is comprised of structural, tumor, and immune cell markers, including eight immunoregulatory proteins that are approved or currently undergoing clinical trials as immunotherapy targets. Here we provide a resource to enable extensive high-dimensional, spatially resolved characterization of the tissue microenvironment across tumor types and imaging modalities. This framework provides researchers with a readily applicable blueprint to study tumor immunology, tissue architecture, and enable mechanistic insights into immunotherapeutic targets.
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影响因子：
9.3
作者：
Ellington AA;Kullo IJ;Bailey KR;Klee GG
通讯作者：
Klee GG
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：
48
作者：
Giesen, Charlotte;Wang, Hao A. O.;Bodenmiller, Bernd
通讯作者：
Bodenmiller, Bernd
影响因子：
13.6
作者：
Keren, Leeat;Bosse, Marc;Angelo, Michael
通讯作者：
Angelo, Michael
影响因子：
82.9
作者：
通讯作者：
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