干旱区生态环境知识资源中心(Arid): Establishing standardized immune phenotyping of metastatic melanoma by digital pathology

Arid

DOI	10.1038/s41374-021-00653-y
	Establishing standardized immune phenotyping of metastatic melanoma by digital pathology
	Sobottka, Bettina; Nowak, Marta; Frei, Anja Laura; Haberecker, Martina; Merki, Samuel; Levesque, Mitchell P.; Dummer, Reinhard; Moch, Holger; Koelzer, Viktor Hendrik
通讯作者	Sobottka, B ; Koelzer, VH (corresponding author), Univ Hosp Zurich, Dept Pathol & Mol Pathol, Zurich, Switzerland.
来源期刊	LABORATORY INVESTIGATION
ISSN	0023-6837
EISSN	1530-0307
出版年	2021
英文摘要	CD8+ tumor-infiltrating T cells can be regarded as one of the most relevant predictive biomarkers in immune-oncology. Highly infiltrated tumors, referred to as inflamed (clinically hot), show the most favorable response to immune checkpoint inhibitors in contrast to tumors with a scarce immune infiltrate called immune desert or excluded (clinically cold). Nevertheless, quantitative and reproducible methods examining their prevalence within tumors are lacking. We therefore established a computational diagnostic algorithm to quantitatively measure spatial densities of tumor-infiltrating CD8+ T cells by digital pathology within the three known tumor compartments as recommended by the International Immuno-Oncology Biomarker Working Group in 116 prospective metastatic melanomas of the Swiss Tumor Profiler cohort. Workflow robustness was confirmed in 33 samples of an independent retrospective validation cohort. The introduction of the intratumoral tumor center compartment proved to be most relevant for establishing an immune diagnosis in metastatic disease, independent of metastatic site. Cut-off values for reproducible classification were defined and successfully assigned densities into the respective immune diagnostic category in the validation cohort with high sensitivity, specificity, and precision. We provide a robust diagnostic algorithm based on intratumoral and stromal CD8+ T-cell densities in the tumor center compartment that translates spatial densities of tumor-infiltrating CD8+ T cells into the clinically relevant immune diagnostic categories inflamed, excluded, and desert. The consideration of the intratumoral tumor center compartment allows immune phenotyping in the clinically highly relevant setting of metastatic lesions, even if the invasive margin compartment is not captured in biopsy material. The authors present a robust diagnostic algorithm based on digital pathology and image analysis that quantifies intratumoral and stromal CD8+ T-cell densities in the tumor center and invasive margin compartment in metastatic melanoma. Spatial CD8+ T-cell densities are translated into the clinically relevant immune diagnostic categories inflamed, excluded, and desert. Their approach also allows efficient immune phenotyping of metastatic lesions, on biopsy material or even in the absence of material from the invasive margin.
类型	Article ; Early Access
语种	英语
收录类别	SCI-E
WOS记录号	WOS:000689531700002
WOS关键词	TUMOR-INFILTRATING LYMPHOCYTES ; COMBINED NIVOLUMAB ; IPILIMUMAB ; BIOMARKER
WOS类目	Medicine, Research & Experimental ; Pathology
WOS研究方向	Research & Experimental Medicine ; Pathology
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/364086
作者单位	[Sobottka, Bettina; Nowak, Marta; Frei, Anja Laura; Haberecker, Martina; Merki, Samuel; Moch, Holger; Koelzer, Viktor Hendrik] Univ Hosp Zurich, Dept Pathol & Mol Pathol, Zurich, Switzerland; [Levesque, Mitchell P.; Dummer, Reinhard] Univ Hosp Zurich, Dept Dermatol, Zurich, Switzerland
推荐引用方式 GB/T 7714	Sobottka, Bettina,Nowak, Marta,Frei, Anja Laura,et al. Establishing standardized immune phenotyping of metastatic melanoma by digital pathology[J],2021.
APA	Sobottka, Bettina.,Nowak, Marta.,Frei, Anja Laura.,Haberecker, Martina.,Merki, Samuel.,...&Koelzer, Viktor Hendrik.(2021).Establishing standardized immune phenotyping of metastatic melanoma by digital pathology.LABORATORY INVESTIGATION.
MLA	Sobottka, Bettina,et al."Establishing standardized immune phenotyping of metastatic melanoma by digital pathology".LABORATORY INVESTIGATION (2021).