In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 9536-9536
Abstract:
9536 Background: Cancer-related fibroblasts (CAFs) are important components of the tumor microenvironment (TME) and play a key role in tumor progression. There is growing evidence that CAF levels in tumors are highly correlated with treatment response and prognosis. However, the effect of CAFs on immunotherapy response remains unknown. Methods: RNA-seq and clinical data were downloaded from TCGA and GEO. The SVA package ComBat function was used to remove batch effects. The ssGSEA algorithm was used to assess the level of cell infiltration in each sample. OS (overall survival) and DFS (disease free survival) were analyzed using the Kaplan–Meier method. GO enrichment analysis was used to assess the biological processes of subgroup differential genes. The Tumor Immune Dysfunction and Exclusion (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 and found that almost all IMFRs (immune cells / fibroblasts) are beneficial to the prognosis. This phenomenon is called “CAFs-mediated immune resistance pattern (CMIRP)”. We evaluated the infiltration abundance of 24 types of immune cells and fibroblasts in 1768 NSCLC samples and found that almost all IMFRs (immune cells / fibroblasts) are beneficial to the prognosis. This phenomenon is called “CAFs-mediated immune resistance pattern (CMIRP)”. The prognosis according to CD8+ T cells was not strong, but CD8+ T cells / fibroblasts (CFR) were significant protective prognostic factors [n = 1588; hazard ratio (HR), 0.66; 95% confidence interval (CI), 0.56–0.78; P 〈 0.001]. Multivariate analysis revealed that the CFR was an independent prognostic biomarker. The TCGA pan-cancer cohort confirmed the widespread presence of CMIRP in cancer. We further defined the CFR high and CFR low subgroups. CFR high samples were enriched with immune activation pathways including T cell activation, cytolysis, and antigen presentation, while CFR low was associated with immunosuppression including activation of transforming growth factor β, epithelial-mesenchymal transition, and angiogenesis pathways. Finally, we combined TIDE and submap to speculate that CFR is a potential prognostic marker of immunotherapy for NSCLC. Conclusions: We proposed the term “CMIRP” to shed light on a more accurate assessment of immune status. CFR is a potential marker for prognosis and predictive efficacy of immunotherapy in NSCLC.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2020.38.15_suppl.9536
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2020
detail.hit.zdb_id:
2005181-5
