Development and validation of a computed tomography–based immune ecosystem diversity index as an imaging biomarker in non-small cell lung cancer

• Published in: European radiology Vol. 32; no. 12; pp. 8726 - 8736
• Main Authors: He, Lan, Li, Zhen-Hui, Yan, Li-Xu, Chen, Xin, Sanduleanu, Sebastian, Zhong, Wen-Zhao, Lambin, Phillippe, Ye, Zhao-Xiang, Sun, Ying-Shi, Liu, Yu-Lin, Qu, Jin-Rong, Wu, Lin, Tu, Chang-Ling, Scrivener, Madeleine, Pieters, Thierry, Coche, Emmanuel, Yang, Qian, Yang, Mei, Liang, Chang-Hong, Huang, Yan-Qi, Liu, Zai-Yi
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.12.2022; Springer Nature B.V
• Subjects: Biomarkers; Carcinoma, Non-Small-Cell Lung - pathology; CD3 antigen; CD4 antigen; CD8 antigen; CD8-Positive T-Lymphocytes - pathology; Computed tomography; Diagnostic Radiology; Ecosystem; Ecosystems; Feature extraction; Humans; Imaging; Imaging Informatics and Artificial Intelligence; Immune status; Immunohistochemistry; Internal Medicine; Interventional Radiology; Lung cancer; Lung Neoplasms - pathology; Lymphocytes; Lymphocytes T; Medical imaging; Medical prognosis; Medicine; Medicine & Public Health; Microenvironments; Neoplasm Staging; Neuroradiology; Non-small cell lung carcinoma; Paraffin; Paraffins; Patients; Prognosis; Radiology; Retrospective Studies; Small cell lung carcinoma; Survival; Tomography; Tomography, X-Ray Computed; Tumor Microenvironment; Tumors; Ultrasound; Immunohistochemistry; Prognosis; Computed tomography; Ecosystem; Non-small cell lung cancer
• ISSN: 1432-1084; 0938-7994; 1432-1084
• DOI: 10.1007/s00330-022-08873-6

Objectives To date, there are no data on the noninvasive surrogate of intratumoural immune status that could be prognostic of survival outcomes in non-small cell lung cancer (NSCLC). We aimed to develop and validate the immune ecosystem diversity index (iEDI), an imaging biomarker, to indicate the intratumoural immune status in NSCLC. We further investigated the clinical relevance of the biomarker for survival prediction. Methods In this retrospective study, two independent NSCLC cohorts (Resec1, n = 149; Resec2, n = 97) were included to develop and validate the iEDI to classify the intratumoural immune status. Paraffin-embedded resected specimens in Resec1 and Resec2 were stained by immunohistochemistry, and the density percentiles of CD3 + , CD4 + , and CD8 + T cells to all cells were quantified to estimate intratumoural immune status. Then, EDI features were extracted using preoperative computed tomography to develop an imaging biomarker, called iEDI, to determine the immune status. The prognostic value of iEDI was investigated on NSCLC patients receiving surgical resection (Resec1; Resec2; internal cohort Resec3, n = 419; external cohort Resec4, n = 96; and TCIA cohort Resec5, n = 55). Results iEDI successfully classified immune status in Resec1 (AUC 0.771, 95% confidence interval [CI] 0.759–0.783; and 0.770 through internal validation) and Resec2 (0.669, 0.647–0.691). Patients with higher iEDI-score had longer overall survival (OS) in Resec3 (unadjusted hazard ratio 0.335, 95%CI 0.206–0.546, p < 0.001), Resec4 (0.199, 0.040–1.000, p < 0.001), and TCIA (0.303, 0.098–0.944, p = 0.001). Conclusions iEDI is a non-invasive surrogate of intratumoural immune status and prognostic of OS for NSCLC patients receiving surgical resection. Key Points • Decoding tumour immune microenvironment enables advanced biomarkers identification. • Immune ecosystem diversity index characterises intratumoural immune status noninvasively. • Immune ecosystem diversity index is prognostic for NSCLC patients.