Comprehensive whole-transcriptome digital spatial profiling of tumor microenvironment remodeling following KN026 treatment

KN026 is a novel bispecific HER2-targeted antibody and confers a promising clinical benefit to HER2-positive breast cancer patients in our phase II clinical trial. The de novo mutation events only tended to explain the driver potentials. In order to elucidate subsequent changes in downstream pathways, using whole-transcriptome digital spatial profiling (DSP), we defined spatial multimolecular dynamic changes following KN026 treatment, including intensive crosstalks between HER2 and bypass signalings within tumor cells, and reversion of suppressive states in immune cells especially tumor infiltrating T and B lymphocytes, which interpreted the potential mechanism of the common efficacy regardless of HR status. Our work provides novel and detailed mechanistic insights into the superiority of KN026 efficacy, not only for the identification of advantageous populations, but also contributing towards combination strategy with endocrine therapy for advanced HER2- and HR- double positive breast cancer.