Genetically engineered ErbB2 overexpression sensitizes organoid-derived tumors to checkpoint inhibition in a syngeneic model of gastric cancer.

ABSTRACT:

Background

ERBB2/HER2 is overexpressed or mutated in ~15% of gastric cancers due to amplification or mutation of the ERBB2 locus. While the tumor cell-intrinsic consequences of ERBB2 overexpression are well understood, much less is known about its effects on the tumor microenvironment.

Methods

We have developed genetically engineered ectopic and orthotopic syngeneic models of organoid-based gastric cancer that have allowed us to study the tumor microenvironment of ErbB2-overexpressing tumors, using spectral flow cytometry, single cell RNA sequencing, and TCR repertoire sequencing. Interventions such as anti-Erbb2 and anti-PD1 antibody treatments were used as well.

Results

We find that ErbB2 drives the infiltration of CD4⁺ and CD8⁺ T-cells,

SUBMITTER: He J 

PROVIDER: S-EPMC12911747 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature