Posted: Friday, November 18, 2022
Hiroki Murai, PhD, of Osaka University, Japan, and colleagues identified a subclass of molecules found in the tumor immune microenvironment of patients with hepatocellular carcinoma that may be targeted with anti–PD-L1 (atezolizumab) plus anti-VEGF (bevacizumab) therapy. These findings were presented at the 2022 American Association for the Study of Liver Diseases (AASLD) Annual Meeting (Abstract 192).
“Steatotic hepatocellular carcinoma was characterized by immune-exhaustion and VEGF signaling activation, leading to high susceptibility to atezolizumab/bevacizumab therapy. MRI can be a useful imaging biomarker of the efficacy of atezolizumab/bevacizumab therapy for hepatocellular carcinoma patients,” concluded the study authors.
Tumor tissue samples were taken from a cohort of 113 patients with nonviral hepatocellular carcinoma who had undergone surgical resection. The researchers conducted RNA sequencing of all samples and sequenced cancer genomes of a subset of 55 tumor samples from the cohort. The additional sequencing focused on a group of 69 genes with known recurrent genetic alterations in hepatocellular cancer. The researchers then estimated intratumoral abundance of immune cell types and intratumor immune activity. VEGF signaling pathway activity was analyzed using single-set gene set enrichment analysis.
Patients were assigned to a VEGF-high or VEGF-low group based on VEGF signaling pathway activity. Significantly fewer telomerase reverse transcriptase and catenin beta-1 mutations were found in the VEGF-high group compared with the VEGF-low group. The sole independent predictors of VEGF-high classification were the lack of diabetes and the presence of steatotic hepatocellular carcinoma. Intratumor immune activity was used to classify patients as “immune-hot” (38%) or “immune-cold “(62%). Immune-hot patients exhibited a significantly lower frequency of catenin beta-1 mutations compared with the immune-cold class. Steatotic hepatocellular carcinoma was the independent predictor of immune-hot classification and was present in 23% of the patients.
Finally, MRI chemical shift imaging was used to identify the presence or absence of steatotic hepatocellular carcinoma in 30 patients with advanced hepatocellular carcinoma who underwent atezolizumab plus bevacizumab therapy. Of them, the 7 steatotic patients had significantly longer progression-free survival than the remaining 23 nonsteatotic patients.
Disclosure: To view the study authors’ disclosures, visit aasld.org.