Advantage and Core Benefit
- Non-invasive Evaluation: MRI enables non-invasive assessment of immune dynamics in liver cancer tissue
- Mechanism-based Diagnosis: Identifies the relationship between palmitic acid accumulation and immune exhaustion, providing a mechanistically grounded imaging approach
- Optimized Therapy Selection: Supports appropriate treatment decisions by distinguishing suitability for combination immunotherapy or multikinase inhibitor therapy
Background and Technology
Hepatocellular carcinoma (HCC) treatment options include immune checkpoint inhibitors (ICIs), multikinase inhibitors, and anti-angiogenic agents. However, the objective response rate (ORR) of these agents remains around 30%, highlighting the need for biomarkers that guide more effective therapeutic choices. Although the tumor immune profile is considered reflective of ICI responsiveness, it is clinically difficult to evaluate immune status through pre-treatment tumor biopsy, as treatment decisions are usually based on imaging diagnosis.
The inventors discovered that approximately 23% of HCCs exhibit high fat content, and these “steatotic” HCCs are associated with an immunosuppressive tumor microenvironment, characterized by T cell exhaustion, infiltration of M2 macrophages and cancer-associated fibroblasts (CAFs), elevated PD-L1 expression on tumor cells, and activation of TGF-β signaling. By assessing hepatic fat deposition via MRI, the researchers found that patients with steatotic HCC who received ICI therapy showed a 100% progression-free survival rate and disease control rate (doi: 10.1002/hep.32573). This suggests that steatotic HCCs identifiable by MRI could serve as predictive imaging biomarkers for immunotherapy responsiveness. Furthermore, steatotic HCCs exhibited significantly shorter median progression-free survival and lower disease control rates under Lenvatinib treatment compared to non-steatotic HCCs. These findings indicate the potential utility of MRI-based fat quantification in determining suitability for either combination immunotherapy or multikinase inhibitor therapy.
Data
- PD-L1 expression was upregulated in tumor tissues of steatotic HCC patients (A, B). MRI (in-phase/opposite-phase) images enabled quantification of hepatic fat content equivalent to histological staining (C, D)
- Patients with steatotic HCC receiving atezolizumab (anti–PD-L1 antibody) + bevacizumab (anti–VEGF antibody) combination therapy achieved 100% disease control and significantly longer progression-free survival (E, F)
- Steatotic HCC patients treated with Lenvatinib showed shorter progression-free survival and lower disease control compared to non-steatotic cases.
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Patent
WO2023210752 and a related patent
Researcher
Dr. Naohiro Kodama (University of Osaka)
Expectations
Seeking licensing opportunities with pharmaceutical companies developing therapies for liver cancer or CROs with expertise in imaging diagnostics, for use as a biomarker to stratify patients. Open to collaborations with developers of imaging analysis software to create diagnostic tools for liver cancer.
Project ID: WL-04261a