Hydralazine Induced Immunologic Response by scRNA-Seq with Olink Proteomics Associated with Survival Time of pancreatic cancer

Background: Pancreatic cancer is a highly lethal cancer with no treatment options when diagnosed at an advanced stage. Hapten combined with chemotherapy drugs have been successfully injected into the tumor for local treatment of pancreatic cancer, but due to the heterogeneity of the tumor, the survival time of patients with similar stages is different. Methods: SCNA-SEQ and Olink proteomics methods were used to observe the cell and genome changes in the survival group treated with hyrazine combined with HEIC for more than 10 months and less than 6 months. scRNA-Seq shows T cell activity of cDCs and polygene-expressed pDCs. Results: scRNA-Seq confirmed the initiation of immune response: NaiveT and CD8Teff increased, proliferation increased, NK decreased, and ribosomal protein gene upregulated after treatment. The Neutrophils_4 gene set score of precursor cell neutrophilS_4 was higher. There was high expression of interferon-stimulating gene in neutrophils s_3, and high expression of s_3 characteristic gene set in interferon-associated neutrophils. Due to immune action, proteomic results showed that GZMB, GZMZ, IL18, CASP-8, CD8A, HO-1 and AOA genes were up-regulated by 8%. DCN, MCP-1, CX3cl1, CD40, CD27, IL33, TIE2, Gal-9, PGE, MCP-3, CD28, PD-L1, CD38, CCL3, MCP-2, MMP7, laptgf-β-1 genes were down-regulated by 18%. Conclusions: Overall, the study showed that patients with similar stages of pancreatic cancer had an enhanced immune response after the same regimen of HEIC treatment, and found that gene expression increased by 8% and decreased by 18% in the longer survival group compared with the shorter survival group due to tumor heterogeneity.