Neoantigen architectures define immunogenicity and drive immune evasion of tumors with heterogenous neoantigen expression.

ABSTRACT:

Background

Intratumoral heterogeneity (ITH) and subclonal antigen expression blunt antitumor immunity and are associated with poor responses to immune-checkpoint blockade immunotherapy (ICB) in patients with cancer. The underlying mechanisms however thus far remained elusive, preventing the design of novel treatment approaches for patients with high ITH tumors.

Methods

We developed a mouse model of lung adenocarcinoma with defined expression of different neoantigens (NeoAg), enabling us to analyze how these impact antitumor T-cell immunity and to study underlying mechanisms. Data from a large cancer patient cohort was used to study whether NeoAg architecture characteristics found to define tumor immunogenicity in our mouse models are linked to ICB responses in patients with

SUBMITTER: Roerden M 

PROVIDER: S-EPMC11552027 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature