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
51P - Enhancing the anti-breast tumour activity of STING through a novel sting transcriptional regulator
Presenter: Hanchu Xiong
Session: Poster display session
Resources:
Abstract
52P - Reverse Warburg effect-related mitochondrial activity and 18F-FDG uptake in invasive ductal carcinoma
Presenter: Byung Wook Choi
Session: Poster display session
Resources:
Abstract
53P - Phase II study of atorvastatin in combination with radiotherapy and temozolomide in patients with glioblastoma (ART): Final analysis report
Presenter: Abdullah Altwairgi
Session: Poster display session
Resources:
Abstract
54P - Association between Parkinson’s disease and brain tumours: A nationwide population-based cohort study
Presenter: Joo-hyun Park
Session: Poster display session
Resources:
Abstract
55P - Toxicity profiles of treatment with modern fractionated radiotherapy, contemporary stereotactic radiosurgery, or transsphenoidal surgery in non-functioning pituitary macroadenoma
Presenter: Kevin Sheng-Po Yuan
Session: Poster display session
Resources:
Abstract
56P - Hippocampal avoidance in WBRT for metastases: Comparative neurocognitive and dosimetric assessment
Presenter: Vibhay Pareek
Session: Poster display session
Resources:
Abstract
57P - Multidisciplinary brain metastasis clinic: Is it effective and worthwhile?
Presenter: Annu Rajpurohit
Session: Poster display session
Resources:
Abstract
58P - Functional status as a determinant prognostic factor for overall survival in adult patients with medulloblastoma treated with chemotherapy and radiotherapy
Presenter: Juan Ayala Alvarez
Session: Poster display session
Resources:
Abstract
59P - Pattern of care in high-grade gliomas after recurrence
Presenter: Nandini Menon
Session: Poster display session
Resources:
Abstract
60P - Five fractions plus “SRS” boost combined with temozolamide for newly diagnosed and recurrent glioblastoma multiforme (GBM)
Presenter: Azhar Rashid
Session: Poster display session
Resources:
Abstract