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Updated: Oct 26, 2025
Immunophenotyping of Orthotopic Homograft Syngeneic of Murine Primary KPC Pancreatic Ductal Adenocarcinoma by Flow Cytometry
Published on: October 9, 2018
Identification and Validation of Immune Molecular Subtypes in Pancreatic Ductal Adenocarcinoma: Implications for
Ruiyu Li1, Yangzhige He2, Hui Zhang1
1Department of Pathology, State Key Laboratory of Complex Severe and Rare Disease, Molecular Pathology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Background:
Pancreatic ductal adenocarcinoma (PDAC) remains treatment refractory. Immunotherapy has achieved success in the treatment of multiple malignancies. However, the efficacy of immunotherapy in PDAC is limited by a lack of promising biomarkers. In this research, we aimed to identify robust immune molecular subtypes of PDAC to facilitate prognosis prediction and patient selection for immunotherapy.
Methods:
A training cohort of 149 PDAC samples from The Cancer Genome Atlas (TCGA) with mRNA expression data was analyzed. By means of non-negative matrix factorization (NMF), we virtually dissected the immune-related signals from bulk gene expression data. Detailed immunogenomic and survival analyses of the immune molecular subtypes were conducted to determine their biological and clinical relevance. Validation was performed in five independent datasets on a total of 615 samples.
Results:
Approximately 31% of PDAC samples (46/149) had higher immune cell infiltration, more active immune cytolytic activity, higher activation of the interferon pathway, a higher tumor mutational burden (TMB), and fewer copy number alterations (CNAs) than the other samples (all P < 0.001). This new molecular subtype was named Immune Class, which served as an independent favorable prognostic factor for overall survival (hazard ratio, 0.56; 95% confidence interval, 0.33-0.97). Immune Class in cooperation with previously reported tumor and stroma classifications had a cumulative effect on PDAC prognostic stratification. Moreover, programmed cell death-1 (PD-1) inhibitors showed potential efficacy for Immune Class (P = 0.04). The robustness of our immune molecular subtypes was further verified in the validation cohort.
Conclusions:
By capturing immune-related signals in the PDAC tumor microenvironment, we reveal a novel molecular subtype, Immune Class. Immune Class serves as an independent favorable prognostic factor for overall survival in PDAC patients.
Insights
Researchers identified a new pancreatic cancer subtype, "Immune Class," characterized by high immune infiltration. This subtype is a favorable prognostic factor and may respond to immunotherapy, including PD-1 inhibitors.
Area of Science:
- Oncology
- Immunology
- Genomics
Background:
- Pancreatic ductal adenocarcinoma (PDAC) is a challenging cancer with limited treatment options.
- Immunotherapy has shown promise in various cancers, but its efficacy in PDAC is hindered by a lack of predictive biomarkers.
- Identifying robust immune molecular subtypes is crucial for improving PDAC prognosis and guiding immunotherapy selection.
Purpose of the Study:
- To identify novel immune molecular subtypes of PDAC.
- To evaluate the prognostic significance of these subtypes.
- To explore their potential role in predicting response to immunotherapy.
Main Methods:
- Non-negative matrix factorization (NMF) was used to analyze mRNA expression data from 149 PDAC samples (TCGA).
- Immunogenomic and survival analyses were performed to characterize identified subtypes.
- Validation was conducted on five independent datasets comprising 615 PDAC samples.
Main Results:
- A distinct molecular subtype, 'Immune Class,' was identified in approximately 31% of PDAC samples.
- Immune Class exhibited higher immune cell infiltration, cytolytic activity, interferon pathway activation, and tumor mutational burden (TMB).
- Immune Class was an independent favorable prognostic factor for overall survival and showed potential sensitivity to PD-1 inhibitors.
Conclusions:
- A novel PDAC molecular subtype, Immune Class, was discovered by analyzing immune signals within the tumor microenvironment.
- Immune Class serves as a significant independent prognostic factor for overall survival in PDAC patients.
- This subtype holds potential for patient stratification and guiding immunotherapy strategies in pancreatic cancer.
