In vivo tumor immune microenvironment phenotypes correlate with inflammation and vasculature to predict immunotherapy response.
In vivo tumor immune microenvironment phenotypes correlate with inflammation and vasculature to predict immunotherapy response.
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体内肿瘤免疫微环境表型与炎症和脉管系统相关，以预测免疫疗法反应。
DOI：
10.1038/s41467-022-32738-7
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发表时间：
2022-09-09
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
对免疫疗法的反应可能是可变的和不可预测的。基于病理学的肿瘤“热”和“冷”表型是静态的，仅依赖于单次单部位活检中的T细胞浸润，导致次优治疗反应预测。肿瘤免疫微环境（TiME）内的动态血管事件（肿瘤血管生成、白细胞运输）也影响抗肿瘤免疫和治疗反应。在这里，我们报告了体内动态细胞水平TiME表型，该表型通过非侵入性反射共聚焦显微镜成像将炎症特征与血管特征结合起来。在皮肤癌患者中，我们证明了与基因和蛋白质表达相关的三种主要TiME表型，以及对Toll样受体激动剂免疫治疗的反应。值得注意的是，具有高炎症的表型与免疫刺激特征相关，而具有高脉管系统的表型与血管生成和内皮无反应性特征相关。此外，具有高炎症和低脉管系统的表型证明了最佳的治疗反应。这种将动态脉管系统与炎症整合的非侵入性体内表型分析方法可作为患者对局部免疫治疗反应的可靠预测因子。活检免疫浸润的标准评估不足以准确预测对免疫治疗的反应。在这里，作者表明，反射共聚焦显微镜可用于量化动态血管和炎症特征，以更好地预测皮肤癌的治疗反应。
Response to immunotherapies can be variable and unpredictable. Pathology-based phenotyping of tumors into ‘hot’ and ‘cold’ is static, relying solely on T-cell infiltration in single-time single-site biopsies, resulting in suboptimal treatment response prediction. Dynamic vascular events (tumor angiogenesis, leukocyte trafficking) within tumor immune microenvironment (TiME) also influence anti-tumor immunity and treatment response. Here, we report dynamic cellular-level TiME phenotyping in vivo that combines inflammation profiles with vascular features through non-invasive reflectance confocal microscopic imaging. In skin cancer patients, we demonstrate three main TiME phenotypes that correlate with gene and protein expression, and response to toll-like receptor agonist immune-therapy. Notably, phenotypes with high inflammation associate with immunostimulatory signatures and those with high vasculature with angiogenic and endothelial anergy signatures. Moreover, phenotypes with high inflammation and low vasculature demonstrate the best treatment response. This non-invasive in vivo phenotyping approach integrating dynamic vasculature with inflammation serves as a reliable predictor of response to topical immune-therapy in patients. Standard assessment of immune infiltration of biopsies is not sufficient to accurately predict response to immunotherapy. Here, the authors show that reflectance confocal microscopy can be used to quantify dynamic vasculature and inflammatory features to better predict treatment response in skin cancers.
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影响因子：
28.2
作者：
Grasso CS;Giannakis M;Wells DK;Hamada T;Mu XJ;Quist M;Nowak JA;Nishihara R;Qian ZR;Inamura K;Morikawa T;Nosho K;Abril-Rodriguez G;Connolly C;Escuin-Ordinas H;Geybels MS;Grady WM;Hsu L;Hu-Lieskovan S;Huyghe JR;Kim YJ;Krystofinski P;Leiserson MDM;Montoya DJ;Nadel BB;Pellegrini M;Pritchard CC;Puig-Saus C;Quist EH;Raphael BJ;Salipante SJ;Shin DS;Shinbrot E;Shirts B;Shukla S;Stanford JL;Sun W;Tsoi J;Upfill-Brown A;Wheeler DA;Wu CJ;Yu M;Zaidi SH;Zaretsky JM;Gabriel SB;Lander ES;Garraway LA;Hudson TJ;Fuchs CS;Ribas A;Ogino S;Peters U
通讯作者：
Peters U
影响因子：
64.8
作者：
Cabrita, Rita;Lauss, Martin;Jonsson, Goran
通讯作者：
Jonsson, Goran
影响因子：
82.9
作者：
Brown, EB;Campbell, RB;Jain, RK
通讯作者：
Jain, RK
影响因子：
24.8
作者：
Dai P;Wang W;Yang N;Serna-Tamayo C;Ricca JM;Zamarin D;Shuman S;Merghoub T;Wolchok JD;Deng L
通讯作者：
Deng L
影响因子：
4.8
作者：
DICE, LR
通讯作者：
DICE, LR