602 Mass spectrometry-based protein biomarker analysis in chemoimmunotherapy combinations identifies unique immune signatures in pancreatic cancer

作者：Marco Tognetti, Nigel Beaton, Kamil Skłodowski, Roland Bruderer, Lukas Reiter · 发表于：Regular and Young Investigator Award Abstracts · 年份：2022 · DOI：10.1136/jitc-2022-sitc2022.0602 · 被引用次数：2 · 研究领域：Pancreatic and Hepatic Oncology Research、Cancer Genomics and Diagnostics、Cancer Immunotherapy and Biomarkers

Background Although the combination of chemotherapy with immunotherapy has led to significant improvements in the treatment of some solid tumors, metastatic pancreatic ductal adenocarcinoma (mPDAC) prognosis has remained largely unaffected by such approaches. Recently, PRINCE, a randomized phase 2 clinical study, reported significantly improved 1-year overall survival (OS) for mPDAC patients treated with nivolumab (nivo)/chemo compared to historical control 1 but not for sotigalimab (sotiga)/chemo or the sotiga/nivo/chemo combination. However, the study identified potential improvement to treatment outcome with patient stratification. 2 Here, we report an unbiased mass spectrometry (MS)-based proteomics profiling of a subset of plasma samples from the PRINCE trial. Methods Plasma proteomic profiling was conducted on PRINCE nivo/chemo and sotiga/chemo longitudinal samples (n = 211, 62 individuals) using Biognosys ultradeep plasma workflow. Briefly, plasma samples were depleted, digested to tryptic peptides, measured by MS/MS and quantified using Spectronaut (Biognosys). Data was investigated for both protein and peptide biomarker with an emphasis on baseline biomarkers associated with clinical outcomes. Results Plasma profiling identified 1,662 proteins and 17,451 modified peptides across the cohorts. First, we developed a model that identified the pharmacodynamic effects of treatment in individual patients. In accordance with the PRINCE study and among the major model ...