Journal
PHARMACEUTICALS
Volume 15, Issue 5, Pages -Publisher
MDPI
DOI: 10.3390/ph15050605
Keywords
esophageal adenocarcinoma; immune checkpoint inhibitors; molecular subtypes; immunotherapy response
Categories
Funding
- National Natural Science Foundation of China [81901687, U20A20369]
- Science, Technology and Innovation Commission of Shenzhen Municipality [JCYJ20190807154819245]
- Key Incubation Fund of SYSU [19ykzd29]
Ask authors/readers for more resources
This study identified two distinct subtypes of esophageal adenocarcinoma (EAC) with significant prognostic differences and differences in tumor microenvironments. The findings suggest that EAC patients of subtype 2 may benefit from PD-1 blockade therapy, while patients of subtype 1 are more responsive to chemotherapy or combination therapy.
A low response rate limits the application of immune checkpoint inhibitors (ICIs) in the treatment of esophageal adenocarcinoma (EAC), which requires the precise characterization of heterogeneous tumor microenvironments. This study aimed to identify the molecular features and tumor microenvironment compositions of EAC to facilitate patient stratification and provide novel strategies to improve clinical outcomes. Here, we performed consensus molecular subtyping with nonnegative matrix factorization (NMF) using EAC data from the Cancer Genome Atlas (TCGA) and identified two distinct subtypes with significant prognostic differences and differences in tumor microenvironments. The findings were further validated in independent EAC cohorts and potential response to ICI therapy was estimated using Tumor Immune Dysfunction and Exclusion (TIDE) and SubMap methods. Our findings suggest that EAC patients of subtype 2 with low levels of cancer-associated fibroblasts, tumor associated macrophages (TAMs), and MDSCs in the tumor microenvironment may benefit from PD-1 blockade therapy, while patients of subtype 1 are more responsive to chemotherapy or combination therapy. These findings might improve our understanding of immunotherapy efficacy and be useful in the development of new strategies to better guide immunotherapy and targeted therapy in the treatment of EAC.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available