小柯机器人

近日，美国基因泰克公司Christine Moussion团队发现，原位肿瘤阵列揭示癌症免疫的早期环境控制。2023年5月31日，国际知名学术期刊《自然》在线发表了这一成果。

研究人员报道了微孔皮肤肿瘤阵列（STAMP），一种将高通量时间推移成像与肿瘤阵列的下一代测序相结合的临床前方法。利用STAMP，研究人员在体内跟踪了数千个阵列肿瘤的发展，以显示肿瘤免疫表型和结果在相邻的肿瘤之间有所不同，并受肿瘤微环境中的局部因素控制。特别是，成纤维细胞和单核细胞招募T细胞进入肿瘤核心是支持T细胞的细胞毒性活动和肿瘤排斥。肿瘤免疫表型随着时间的推移是动态的，早期转化为免疫炎症表型可以预测自发的或治疗诱导的肿瘤排斥反应。因此，STAMP捕捉到了肿瘤排斥的空间、细胞和分子成分的动态关系，有可能将治疗概念转化为成功的临床策略。

据了解，肿瘤的免疫表型是预测其对免疫治疗反应的一个关键因素。对检查点阻断疗法有反应的患者通常表现为T细胞高度浸润的免疫性炎症肿瘤。然而，并非所有发炎的肿瘤都对治疗有反应，甚至在缺乏T细胞（免疫沙漠）或在空间上将T细胞排除在肿瘤病变外围（免疫排除）的肿瘤中，反应率更低。尽管这些肿瘤免疫表型对患者很重要，但由于在原位追踪这些特征的技术难度，人们对它们的发展、异质性或动态变化知之甚少。

附：英文原文

Title: In situ tumour arrays reveal early environmental control of cancer immunity

Author: Ortiz-Muoz, Guadalupe, Brown, Markus, Carbone, Catherine B., Pechuan-Jorge, Ximo, Rouilly, Vincent, Lindberg, Henrik, Ritter, Alex T., Raghupathi, Gautham, Sun, Qianbo, Nicotra, Tess, Mantri, Shreya R., Yang, Angela, Doerr, Jonas, Nagarkar, Deepti, Darmanis, Spyros, Haley, Benjamin, Mariathasan, Sanjeev, Wang, Yulei, Gomez-Roca, Carlos, de Andrea, Carlos Eduardo, Spigel, David, Wu, Thomas, Delamarre, Lelia, Schneberg, Johannes, Modrusan, Zora, Price, Richard, Turley, Shannon J., Mellman, Ira, Moussion, Christine

Issue&Volume: 2023-05-31

Abstract: The immune phenotype of a tumour is a key predictor of its response to immunotherapy1,2,3,4. Patients who respond to checkpoint blockade generally present with immune-inflamed5,6,7 tumours that are highly infiltrated by T cells. However, not all inflamed tumours respond to therapy, and even lower response rates occur among tumours that lack T cells (immune desert) or that spatially exclude T cells to the periphery of the tumour lesion (immune excluded)8. Despite the importance of these tumour immune phenotypes in patients, little is known about their development, heterogeneity or dynamics owing to the technical difficulty of tracking these features in situ. Here we introduce skin tumour array by microporation (STAMP)—a preclinical approach that combines high-throughput time-lapse imaging with next-generation sequencing of tumour arrays. Using STAMP, we followed the development of thousands of arrayed tumours in vivo to show that tumour immune phenotypes and outcomes vary between adjacent tumours and are controlled by local factors within the tumour microenvironment. Particularly, the recruitment of T cells by fibroblasts and monocytes into the tumour core was supportive of T cell cytotoxic activity and tumour rejection. Tumour immune phenotypes were dynamic over time and an early conversion to an immune-inflamed phenotype was predictive of spontaneous or therapy-induced tumour rejection. Thus, STAMP captures the dynamic relationships of the spatial, cellular and molecular components of tumour rejection and has the potential to translate therapeutic concepts into successful clinical strategies.

DOI: 10.1038/s41586-023-06132-2

Source: https://www.nature.com/articles/s41586-023-06132-2

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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