Abstract 327P
Background
Hepatocellular carcinoma (HCC) is one of the most common malignancies in China with poor prognosis. Recently, personalized neoantigen-based immunotherapy has been reported to induce robust anti-tumor immune responses to facilitate tumor rejection in several solid tumors. However, whether it possess therapeutic potential in HCC still remain unclear. Thus, a systemic understanding of neoantigen burden (TNB) in HCC microenvironment is in need.
Methods
HCC and matched peritumor tissue collected from 59 HCC patients were subjected to DNA and RNA sequencing for identifying tumor associated neoantigens. Then the association between neoantigens and clinical features, immune signatures, as well as clonal evolution patterns in HCC were evaluated.
Results
In enrolled HCC patients, a median of 106 somatic mutations and 15 neoantigens were identified in each patient. TNB was significantly correlated with tumor somatic mutation burden (R2 = 0.893, P = 3.0 × 10^-24). Furthermore, the clinicopathological analysis revealed that patients with higher TNB was characterized with older age (p = 0.006), decreased tumor size (p = 0.020) and lower recurrence rate (p = 0.019). Additionally, TNB was also significantly associated with relapse free survival (P = 0.033) and overall survival (P = 0.022) in HCC patients. Surprisingly, HCC tumor with high immune cell infiltration were more likely to have no tumor envelope (P = 0.027) and resulted in shorter overall survival time after surgery (P = 0.025); the patients with lower immune cell signatures related to antigen-processing have relatively higher TNB in HCC. Meanwhile, clonal evolution analysis revealed that the clonal mutations were more likely to be neoantigens ( P = 9.2 × 10^-5) than subclonal mutations, suggesting higher immunogenicity for clonal mutations. And tumors with higher proportion of neoantigens in clonal mutations were more likely to involved in clonal evolution, which may due to the immunoediting of neoantigens (P = 0.002).
Conclusions
Our results demonstrated that neoantigens play an important role in tumor clonal evolution and immune response in HCC, which could provide insights for future HCC immunotherapy.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
64P - Entrectinib in locally advanced/metastatic ROS1 and NTRK fusion-positive non-small cell lung cancer (NSCLC): Updated integrated analysis of STARTRK-2, STARTRK-1 and ALKA-372-001
Presenter: Filippo de Braud
Session: Poster display session
Resources:
Abstract
65P - Updated efficacy and safety of entrectinib in patients with NTRK fusion-positive tumours: Integrated analysis of STARTRK-2, STARTRK-1 and ALKA-372-001
Presenter: Christian Rolfo
Session: Poster display session
Resources:
Abstract
66P - Brain metastases, treatment patterns and outcomes in ROS1-positive NSCLC patients from US oncology community centers
Presenter: Matthew Krebs
Session: Poster display session
Resources:
Abstract
67P - Pooled safety analysis of tepotinib in Asian patients with advanced solid tumours
Presenter: Kentaro Yamazaki
Session: Poster display session
Resources:
Abstract
68P - A novel anti-EGFR antibody HLX07 for potential treatment of squamous cell carcinoma of the head and neck
Presenter: Ming Mo Hou
Session: Poster display session
Resources:
Abstract
69P - Irinotecan and cisplatin therapy-induced neutropenia as a prognostic factor in patients with extensive-disease small cell lung cancer
Presenter: Hiroshi Ishikawa
Session: Poster display session
Resources:
Abstract
70P - Is safe and efficient by intraoperative endoscopic nasobiliary drainage over primary closure of the common bile duct for cholecystolithiasis combined with common bile duct stones: A meta-analysis
Presenter: Jiasheng Cao
Session: Poster display session
Resources:
Abstract
71P - Irreversible electroporation versus radiotherapy after induction chemotherapy on survival in patients with locally advanced pancreatic cancer: A propensity score analysis
Presenter: Chaobin He
Session: Poster display session
Resources:
Abstract
72P - Novel technique of near-focus mode for accurate operation during endoscopic submucosal tunneling procedure: A two-center comparative study
Presenter: Wei Peng
Session: Poster display session
Resources:
Abstract
73P - Cabozantinib in combination with anti-PD1 immune checkpoint inhibitor in syngeneic tumour mouse models
Presenter: Rachel Sparks
Session: Poster display session
Resources:
Abstract