Abstract 410: Interaction between CAFs and CD8+ T in non-small cell lung cancer (NSCLC) affects prognosis and efficacy of immunotherapy

Background: Tumor infiltrating stromal cells and immune cells are the main components of the tumor microenvironment. Cancer-associated fibroblasts (CAFs) make up the bulk of cancer stroma and play a key role in tumor progression. Evidence indicates that CAFs are highly related to treatment response...

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Veröffentlicht in:Cancer research (Chicago, Ill.) Ill.), 2020-08, Vol.80 (16_Supplement), p.410-410
Hauptverfasser: Zheng, Xinlong, Zeng, Dongqiang, Li, Pansong, Pen, Wenying, Gao, Xuan, Zhou, Zhipeng, Bai, Jing, Li, Junhui, Ding, Jianming, Wang, Deqiang, Zheng, Suya, Lin, Gen
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Sprache:eng
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Zusammenfassung:Background: Tumor infiltrating stromal cells and immune cells are the main components of the tumor microenvironment. Cancer-associated fibroblasts (CAFs) make up the bulk of cancer stroma and play a key role in tumor progression. Evidence indicates that CAFs are highly related to treatment response and prognosis. However, the effect of CAFs on immunotherapy response still remains unknown. Methods: RNA-seq and clinical data were downloaded from TCGA and GEO. The sva package was used to remove batch effects. The ssGSEA algorithm was used to assess the level of infiltration of 24 immune cells and fibroblasts from each sample. ImmuneScore was calculated using the ESTIMATE method to characterize the degree of immune infiltration. OS and DFS were analyzed using the K-M method. GO enrichment analysis is used to identify the biological process of genes. The TIDE algorithm and subclass mapping were used to predict the clinical response to immune checkpoint blockade. Results: We evaluated the infiltration abundance of 24 types of immune cells and fibroblasts in 1768 NSCLC samples. Positive correlation between immune infiltration and CAFs infiltration through multiple methods (immune cells, Immunescore, and clustering of immune cells) (Kruskal-Wallis and Pearson test, p < 0.05) were found. There were only two types of immune cells in two cohorts are beneficial for prognosis, but the number of IMFRs (Immune cells / CAFs) that are positive correlated with prognosis is more than half of the total number of classes (log-rank test; P < 0.05). Univariate cox regression analysis showed that almost all IMFRs tended to be favorable for prognosis. This phenomenon is called “CAFs-mediated immune resistance pattern (CMIRP)”. At the best cut-off point, patients with high fibroblast content had worse prognosis (log-rank test; P
ISSN:0008-5472
1538-7445
DOI:10.1158/1538-7445.AM2020-410