{
  "abstract": "Background Pancreatic cancer is complicated by many factors, including the unique tumor microenvironment, in which many of the immune cells are pro-tumor macrophages. While tumor macrophage subsets have been studied in pancreatic cancer, there has been little work focused on monocytes, which are macrophage precursors. Monocytes exist in three circulating subsets- classical (CD14+ CD16-), intermediate (CD14+ CD16+), and nonclassical (CD14 low CD16+), each with unique lifespans, recruitment, and functions. While these functions have been studied at homeostasis, there has been less exploration into how they may be altered in pancreatic disease, especially after treatments such as chemotherapy. The goal of this study is to characterize monocyte subsets in pancreatic cancer, establish how they change after chemotherapy, and determine if such changes affect patient outcomes.Methods Blood was collected from patients with untreated pancreatic cancer, pancreatic cancer treated with FOLFIRINOX or gemcitabine-based neoadjuvant chemotherapeutics (post-chemotherapy but prior to surgical resection), or control patients with benign pancreatic disease. Peripheral blood mononuclear cells were isolated by buffy coat and stained for flow cytometric profiling of monocyte subsets via a spectral flow cytometer or FACS sorting of monocyte subsets. Sorted monocyte subsets underwent RNA extraction and subsequent bulk RNA sequencing to compare gene expression in benign, treated, and untreated samples.Results Initial data suggests total monocytes trend toward elevation in pancreatic cancer compared to benign disease. Specifically, intermediate monocytes appear to drive this trend. Total monocytes are further elevated in patients who received neoadjuvant chemotherapy compared to those without treatment. Intermediate monocytes, rather than other monocyte subsets, are significantly elevated after treatment. While patient number is still low, it appears this effect may be more prominent in patients receiving FOLFIRINOX rather than gemcitabine/nab-paclitaxel treatment. Further, preliminary analysis suggests elevated numbers of intermediate monocytes after chemotherapy is linked to lower tumor and nodal disease stage.Conclusions Neoadjuvant chemotherapeutics administered in pancreatic cancer seem to result in a shift in monocyte populations, whereby intermediate monocytes are specifically elevated. Interestingly, this shift appears to be beneficial, resulting in lower disease stage. Ongoing work includes analysis of RNA sequencing to determine if genes suggestive of functional pathways are altered in circulating intermediate monocytes after chemotherapy. Additional work includes an ex vivo study to culture sorted intermediate monocytes with matched extracellular fluid from patient tumors to determine if intermediate monocytes that may be recruited to tumors differentiate into pro-tumor or anti-tumor cell types.Ethics Approval This study obtained IRB approval (2505164691) by the West Virginia University Office for Human Research Protections. All patients gave informed consent prior to taking part in the study.Reference van Elsas MJ, Labrie C, Etzerodt A, Charoentong P, van Stigt Thans JJC, Van Hall T, van der Burg SH. Invasive margin tissue-resident macrophages of high CD163 expression impede responses to T cell-based immunotherapy. J Immunother Cancer 2023;11(3).",
  "authors": [
    {
      "affiliations": [
        "West Virginia University, Morgantown, WV, USA"
      ],
      "name": "Alyson M Stevens"
    },
    {
      "affiliations": [
        "West Virginia University, Morgantown, WV, USA"
      ],
      "name": "Kristen Ranson"
    },
    {
      "affiliations": [
        "West Virginia University, Morgantown, WV, USA"
      ],
      "name": "Cristal Espinosa"
    },
    {
      "affiliations": [
        "West Virginia University, Morgantown, WV, USA"
      ],
      "name": "Brian A Boone"
    },
    {
      "affiliations": [
        "West Virginia University, Morgantown, WV, USA"
      ],
      "name": "Timothy Eubank"
    }
  ],
  "title": "795 Circulating intermediate monocytes are elevated in pancreatic cancer after neoadjuvant chemotherapy",
  "uid": "de032218-d472-52b6-8625-130553cdd046"
}