The impact of PD-1 antibody or G-CSF antibody on the immune system and the hematopoiesis of TNBC mice

Triple negative breast cancer (TNBC) is the most intractable subtype of breast cancer. Inhibitors of programmed cell death protein-1 (PD-1) or its ligand PD-L1 have been considered as promising treatment for TNBC patients. However, only a minor subset of TNBC patients benefits from the monotherapy. An analysis of how PD-1/PD-L1 blockage affect immune activities in TNBC tumor-bearing mice could provide insights for it limitation. G-CSF was known to be highly elevated in TNBC cells, and affecting hematopoiesis and the immune system. Spleen is an immune organ and with extramedullary hematopoiesis in TNBC mice. Here we analyzed splenocyte gene expressions changed by administration of either PD-1 antibody or G-CSF antibody in both 4T1 tumor bearing mice and non-tumor control mice. TNBC tumor significantly changed gene expressions in splenocytes, which is consistent with a significant change in splenocyte composition. These genes were enriched in immune related pathways. Anti-PD-1 antibody treatment had limited impact on spleen immune cells composition and splenocyte gene expressions. The most affected genes were enriched in metabolism and extracellular matrix related pathways. Anti-G-CSF antibody treatment had higher impact on the splenocyte gene expression profile, making it more like the gene expression profile in the non-tumor control mice. Overall design: Mammary pads of Balb/c female mice were orthotopically implanted with 4T1 cells on day 0 and mice were administered with G-CSF antibody, PD-1 antibody, or anti-IgG dissolved in PBS through intraperitoneal on day 18, day 21, day 24 at a dose of 10 mg/kg. At the endpoint of day 29, We collected splenocytes from mice bearing 4T1 tumor or not and performed RNA-seq by using Illumina NovaSpeq 6000 platform.