Back to Search
Start Over
Immune Profiling of Combined Hepatocellular- Cholangiocarcinoma Reveals Distinct Subtypes and Activation of Gene Signatures Predictive of Response to Immunotherapy
- Source :
- Clinical cancer research : an official journal of the American Association for Cancer Research. 28(3)
- Publication Year :
- 2021
-
Abstract
- Purpose: Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare malignancy associated with an overall poor prognosis. We aimed to investigate the immune profile of cHCC-CCA and determine its impact on disease outcome. Experimental Design: We performed a multicenter study of 96 patients with cHCC-CCA. Gene expression profile was analyzed using nCounter PanCancer IO 360 Panel. Densities of main immune cells subsets were quantified from digital slides of IHC stainings. Genetic alterations were investigated using targeted next-generation sequencing. Results: Two main immune subtypes of cHCC-CCA were identified by clustering analysis: an “immune-high” (IH) subtype (57% of the cases) and an “immune-low” (IL) subtype (43% of the cases). Tumors classified as IH showed overexpression of genes related to immune cells recruitment, adaptive and innate immunity, antigen presentation, cytotoxicity, immune suppression, and inflammation (P < 0.0001). IH cHCC-CCAs also displayed activation of gene signatures recently shown to be associated with response to immunotherapy in patients with HCC. Quantification of immunostainings confirmed that IH tumors were also characterized by higher densities of immune cells. Immune subtypes were not associated with any genetic alterations. Finally, multivariate analysis showed that the IH subtype was an independent predictor of improved overall survival. Conclusions: We have identified a subgroup of cHCC-CCA that displays features of an ongoing intratumor immune response, along with an activation of gene signatures predictive of response to immunotherapy in HCC. This tumor subclass is associated with an improved clinical outcome. These findings suggest that a subset of patients with cHCC-CCA may benefit from immunomodulating therapeutic approaches.
- Subjects :
- Adult
Male
Cancer Research
Carcinoma, Hepatocellular
medicine.medical_treatment
Antigen presentation
Inflammation
Malignancy
Subclass
Cholangiocarcinoma
Neoplasms, Multiple Primary
Immune system
medicine
Humans
Aged
Aged, 80 and over
Innate immune system
business.industry
Liver Neoplasms
Immunotherapy
Middle Aged
medicine.disease
Treatment Outcome
Oncology
Bile Duct Neoplasms
Cancer research
Immunohistochemistry
Female
medicine.symptom
business
Forecasting
Subjects
Details
- ISSN :
- 15573265
- Volume :
- 28
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Clinical cancer research : an official journal of the American Association for Cancer Research
- Accession number :
- edsair.doi.dedup.....d3bb10462c583a6d9a49a3eb64496090