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Tumour microenvironment‐based molecular profiling reveals ideal candidates for high‐grade serous ovarian cancer immunotherapy
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Tumour microenvironment‐based molecular profiling reveals ideal candidates for high‐grade serous ovarian cancer immunotherapy
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Journal Article
Tumour microenvironment‐based molecular profiling reveals ideal candidates for high‐grade serous ovarian cancer immunotherapy
2021
Overview
Objective
Due to limited immunological profiles of high‐grade serous ovarian cancer (HGSOC), we aimed to characterize its molecular features to determine whether a specific subset that can respond to immunotherapy exists.
Materials and Methods
A training cohort of 418 HGSOC samples from TCGA was analysed by consensus non‐negative matrix factorization. We correlated the expression patterns with the presence of immune cell infiltrates, immune regulatory molecules and other genomic or epigenetic features. Two independent cohorts containing 482 HGSOCs and in vitro experiments were used for validation.
Results
We identified immune and non‐immune groups where the former was enriched in signatures that reflect immune cells, infiltration and PD‐1 signalling (all, P < 0.001), and presented with a lower chromosomal aberrations but increased neoantigens, tumour mutation burden, and microsatellite instability (all, P < 0.05); this group was further refined into two microenvironment‐based subtypes characterized by either immunoactivation or carcinoma‐associated fibroblasts (CAFs) and distinct prognosis. CAFs‐immune subtype was enriched for factors that mediate immunosuppression and promote tumour progression, including highly expressed stromal signature, TGF‐β signalling, epithelial‐mesenchymal transition and tumour‐associated M2‐polarized macrophages (all, P < 0.001). Robustness of these immune‐specific subtypes was verified in validation cohorts, and in vitro experiments indicated that activated‐immune subtype may benefit from anti‐PD1 antibody therapy (P < 0.05).
Conclusion
Our findings revealed two immune subtypes with different responses to immunotherapy and indicated that some HGSOCs may be susceptible to immunotherapies or combination therapies.
A comprehensive profiling of high‐grade serous ovarian cancer based on multifarious molecular features identified an immune group in high‐grade serous ovarian cancer that contains two robust microenvironment‐based subtypes with distinct likelihoods of response to immunotherapies that may also represent ideal immunotherapy candidates.
Publisher
John Wiley & Sons, Inc,John Wiley and Sons Inc
Subject
/ Biomarkers, Tumor - analysis
/ Biomarkers, Tumor - genetics
/ Cancer
/ Cystadenocarcinoma, Serous - drug therapy
/ Cystadenocarcinoma, Serous - genetics
/ Cystadenocarcinoma, Serous - pathology
/ Epithelial-Mesenchymal Transition - immunology
/ Female
/ Gene Expression Profiling - methods
/ Genomics
/ high‐grade serous ovarian cancer
/ Humans
/ Mutation
/ Original
/ Ovarian Neoplasms - genetics
/ Ovarian Neoplasms - pathology
/ Proteins
/ Transforming growth factor-b
/ Tumor Microenvironment - genetics
/ Tumor Microenvironment - immunology
/ Tumors
