{
  "abstract": "Background Pancreatic cancer is traditionally considered an ‘immune cold’ tumor. Although outcomes have improved dramatically for patients with resectable disease undergoing adjuvant chemotherapy, limited advancement in treating metastatic PDAC has been made. Further, the success of immunotherapy (anti-PD-1 and anti-CTLA-4) in other solid malignancies has not been replicated in PDAC. We evaluated if treatment with gold salts – Aurothiomalate (AM) and Chloroaurate (CA) could induce alter antigen expression on cancer cell surface, turning the immunologically quiescent tumor, ‘hot.’On treatment with 0.1mM AM or CA, we recorded increased cell surface expression of ICOSL (CD275), PDL-1 (CD274) and MHC-1.Methods Murine pancreatic cancer cell line (Panc02-OVA) was employed in our study. Cells were exposed to 0.1mM AM or CA diluted in complete cell media (24 hours) and then irradiated with 6Gy X-ray radiation (RT). 24 hours later, the surface antigen expression of PD-1, ICOSL and MHC-1 was evaluated by flow cytometry.Results ICOSL (Inducible co-stimulatory ligand) is encoded by the ICOSLG gene. It is constitutively expressed by antigen-presenting cells (B cells, macrophages, and dendritic cells) while ICOS is expressed on only a small fraction of resting T cells at low levels after activation. The interaction of ICOSLG with its receptor modulates activation, proliferation, differentiation and subsequent cytokine production by T cells and antibody production in B cells. The ICOS/ICOSLG axis can promote either antitumor (when activated in Th1 and other Teff). Per our results, treatment naïve cells expressed ~1% surface ICOSL, which was augmented to ~5% by both AM and CA, similar to increase by single dose RT (figure 1). Further, AM synergistically with RT increased ICOSL surface expression to ~11% (figure 2).While Pembrolizumab (anti-PD-1) is approved for patients with advanced PDAC with mismatch repair deficient (dMMR) or microsatellite instability high (MSI-H), only a miniscule number are dMMR/MSI-H (0.8%-2%) resulting in marginal therapeutic benefit. Treating Panc02-OVA cells with either AM or CA upregulated PD-1 expression from 3% to 10%, comparable to RT (figure 1). On combination, AM/CA +RT synergistically increased the% of PD-1+ cells (~15%) (figure 2).AM treatment increased MHC-1+ cells and synergistically with RT, induced MHC-1 surface expression greater than AM monotherapy (figures 1, 2). In murine squamous cell carcinoma models, higher tumor MHC-1 expression has correlated with higher tumor regression with Anti PD-L1 immunotherapy.Conclusions Our results indicate that gold salts in combination with RT can remodel the immune profile of immunologically cold pancreatic tumors to confer therapeutic advantage.Abstract 872 Figure 1Effects of gold salt on surface immune marker. Aurothiomalate and Chloroaurate upregulate ICOSL, PDL-1 and MHC-1 expression on pancreatic cancer cellsAbstract 872 Figure 2Synergistic effect of gold salt with RT. Aurothiomalate and Chloroaurate synergize with RT to increase surface expression of immune markers",
  "authors": [
    {
      "affiliations": [
        "The University of Texas Health Science Center at Houston, Houston, TX, USA"
      ],
      "name": "Prapannajeet Biswal"
    },
    {
      "affiliations": [
        "The University of Texas Health Science Center at Houston, Houston, TX, USA"
      ],
      "name": "Khadijeh Koushki"
    },
    {
      "affiliations": [
        "The University of Texas Health Science Center at Houston, Houston, TX, USA"
      ],
      "name": "Bhoomika Muruvekere Lakshmisha"
    },
    {
      "affiliations": [
        "The University of Texas Health Science Center at Houston, Houston, TX, USA"
      ],
      "name": "Prudhvi Chand Mallepaddi"
    },
    {
      "affiliations": [
        "The University of Texas Health Science Center at Houston, Houston, TX, USA"
      ],
      "name": "Arjun B Vasan"
    },
    {
      "affiliations": [
        "The University of Texas Health Science Center at Houston, Houston, TX, USA"
      ],
      "name": "Gabrielle Krouse"
    },
    {
      "affiliations": [
        "The University of Texas Health Science Center at Houston, Houston, TX, USA"
      ],
      "name": "Yuri Mackeyev"
    },
    {
      "affiliations": [
        "The University of Texas Health Science Center at Houston, Houston, TX, USA"
      ],
      "name": "Geraldine Raja"
    },
    {
      "affiliations": [
        "The University of Texas Health Science Center at Houston, Houston, TX, USA"
      ],
      "name": "Sunil Krishnan"
    }
  ],
  "title": "872 Systemically administered gold salts can transform ‘immune cold’ pancreatic cancers ‘hot’ to potentiate current and future immmunologics",
  "uid": "6e1e0fe6-83b4-5623-9f54-dbed66cf4b10"
}