Recent studies have uncovered the co-existence of basal and classical subtypes within pancreatic ductal adenocarcinoma (PDAC). We sought to characterize these intermediary cells using single-cell RNA sequencing of PDAC. We performed subtyping on 18 single-cell RNA sequencing human PDAC samples to identify multiple intermediary subtypes. We compared single-cell profiling of patient-matched blood and tumor samples to measure changes in the local and systemic immune microenvironments in <a href="https://www.ncbi.nlm.nih.gov/gene/3576">CXCL8</a>-high tumors vs. CXCL8-low tumors. Finally, we leveraged longitudinally patient-matched blood over the course of chemotherapy. In our studies we identified a cluster of <a href="https://www.ncbi.nlm.nih.gov/gene/3872">KRT17</a>high intermediary cancer cells that uniquely express high levels of CXCL8 and other cytokines which in turn influence the myeloid compartment both locally and systemically. We utilized sequencing data from dbGaP study accession <a href="https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs002070">phs002070</a>. In addition to that, we included sequencing from new specimens which are deposited to this submission, consisting of one additional tumor specimen and 5 PBMC samples, sequenced after chemotherapy (longitudinally matched to PBMC samples in phs002071.v1.p1). FASTQ files of these sequencing runs are available through this dbGaP submission.

KRT17High/CXCL8+ Tumor Cells Display Both Classical and Basal Features    and Regulate Myeloid Infiltration in the Pancreatic Cancer    Microenvironment