GITR and TIGIT immunotherapy provokes divergent multicellular responses in the tumor microenvironment of gastrointestinal cancers.

ABSTRACT:

Background

Understanding the mechanistic effects of novel immunotherapy agents is critical to improving their successful clinical translation. These effects need to be studied in preclinical models that maintain the heterogenous tumor microenvironment (TME) and dysfunctional cell states found in a patient's tumor. We investigated immunotherapy perturbations targeting co-stimulatory molecule GITR and co-inhibitory immune checkpoint TIGIT in a patient-derived ex vivo system that maintains the TME in its near-native state. Leveraging single-cell genomics, we identified cell type-specific transcriptional reprogramming in response to immunotherapy perturbations.

Methods

We generated ex vivo tumor slice cultures from fresh surgical resections of gastric and colon cancer and treate

SUBMITTER: Sathe A 

PROVIDER: S-EPMC10680277 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature