PRJNA795151
Tumor-targeted interleukin-12 synergizes with entinostat to overcome PD-1/PD-L1 blockade-resistant tumors harboring MHC-I and APM deficiencies
Immune checkpoint blockade (ICB) has achieved unprecedented success in treating multiple cancer types. However, clinical benefit remains modest for most patients with solid malignancies due to primary or acquired resistance. Tumor-intrinsic loss of MHC class I (MHC-I) and aberrations in antigen processing machinery (APM) and interferon gamma (IFNg) pathways have been shown to play an important role in ICB resistance. While a plethora of combination treatments are being investigated to overcome ICB resistance, there are few identified preclinical models of solid tumors harboring these deficiencies to explore therapeutic interventions that can bypass ICB resistance. Here, we investigated the combination of the epigenetic modulator entinostat and the tumor-targeted immunocytokine NHS-IL12 in three different murine tumor models resistant to PD1/PDL1 inhibitors and harboring MHC-I, APM, and IFNg response deficiencies and differing tumor mutational burden (TMB). This BioProject provides bulk RNA-Seq data from TC1/a9 tumors grown in vivo in syngeneic mice (C57/BL6) treated with PBS, entinostat, NHS/IL-12 or a combination (entinostat and NHS/IL-12). Whole exome sequencing data is also provided from untreated murine tumor cell lines (TC1/a9, CMT.64, and RVP3), as well as normal tissue (tail) from C57/BL6.