Divergent response to radio-immunotherapy is defined by intrinsic features of the tumor microenvironment.

ABSTRACT:

Background

Treatment with immunotherapy can elicit varying responses across cancer types, and the mechanistic underpinnings that contribute to response vrsus progression remain poorly understood. However, to date there are few preclinical models that accurately represent these disparate disease scenarios.

Methods

Using combinatorial radio-immunotherapy consisting of PD-1 blockade, IL2Rβγ biased signaling, and OX40 agonism we were able to generate preclinical tumor models with conflicting responses, where head and neck squamous cell carcinoma (HNSCC) models respond and pancreatic ductal adenocarcinoma (PDAC) progresses.

Results

By modeling these disparate states, we find that regulatory T cells (Tregs) are expanded in PDAC tumors undergoing treatment, constraining tumo

SUBMITTER: Gadwa J 

PROVIDER: S-EPMC11749720 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature