NOTCH1 inhibition enhances immunogenicity and sensitizes triple-negative breast cancer to immune checkpoint inhibitors.

ABSTRACT: Although immune checkpoint inhibitors (ICIs) have elicited desirable clinical outcomes, their effective application remains an obstacle due to immunologically "cold" tumors that manifest lymphocyte exhaustion or poor infiltration. Hence, exploring new therapeutic strategies to enhance antitumor immunity is important. NOTCH1 has emerged as an oncogene in multiple malignancies and is involved in regulating the tumor microenvironment (TME). Here, we demonstrated that NOTCH1 inhibition enhanced the expression of MHC class I (MHC-I) molecules and antigen presentation-related genes and increased the characteristics of immunogenic cell death (ICD), including calreticulin (CALR) translocation, ATP release, and endoplasmic reticulum (ER) stress signaling activation. These events enhance tumor antig

SUBMITTER: Gao Y 

PROVIDER: S-EPMC12105136 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature