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| Home > Publications database > Intratumoral abundance of M2-macrophages is associated with unfavorable prognosis and markers of T-cell exhaustion in small cell lung cancer patients. |
| Home > Publications database > Intratumoral abundance of M2-macrophages is associated with unfavorable prognosis and markers of T-cell exhaustion in small cell lung cancer patients. |
| Journal Article | DKFZ-2023-01379 |
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2023
Nature Publishing Group
London
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Please use a persistent id in citations: doi:10.1016/j.modpat.2023.100272
Abstract: Small cell lung cancer (SCLC) accounts for about 10-15% of lung cancer cases. Unlike non-SCLC, therapy options for SCLC are limited, reflected by a five-year survival rate of about 7%. At the same time, the rise of immunotherapeutic approaches in cancer therapy has rationalized to account for inflammatory phenotypes in tumors. However, the composition of the inflammatory microenvironment in human SCLC is poorly understood to date. In our study, we used in-depth image analysis of virtual whole-slide-images of 45 SCLC tumors and evaluated different markers of M2-macrophages (CD163, CD204) together with global immunological markers (CD4, CD8, CD68, CD38, FOXP3, CD20) and characterized their abundance intratumorally using quantitative image analysis, combined with a deep-learning model for tumor segmentation. In addition, independent scoring, blinded to the results of the computational analysis, was performed by an expert pathologist of both CD163/CD204 and PD-L1. To this end, we evaluated the prognostic relevance of the abundance of these cell types to overall survival. Given a two-tier threshold of the median of the M2 marker CD163 within the study population, there was a 12 month overall survival rate of 22% [95% CI=10-47%] for patients with high CD163 abundance and 41% [95% CI=25-68%] for patients with low CD163 counts. Patients with increased CD163 had a median overall survival of 3 months compared to 8.34 months for patients with decreased CD163 counts (p=0.039) - which could be confirmed by expert pathologist (p=0.018). By analyzing cases with increased CD163 cell infiltrates, a trend for higher FOXP3 counts and PD-L1 positive cells, together with increased CD8 T-cell infiltrates were observed - which could be confirmed using an independent cohort on transcriptional level. Together, we showed that markers of M2 were associated with unfavorable outcome in our study cohort.
Keyword(s): CD163 ; M2 ; SCLC ; Small cell lung cancer ; TME ; biomarker ; lung cancer ; macrophages ; tumor microenvironment
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