{
  "abstract": "Background Type 1 conventional dendritic cell (cDC1) therapy is a novel pre-clinical cell therapy that elicits systemic immunity in multiple murine tumor models and augments response to immune checkpoint blockade (ICB). 1–3 cDC1s possess the ability to migrate from tumors to tumor-draining lymph nodes (tdLNs) through expression of chemokine receptors such as CCR7, an important process for cDC1-mediated priming of naïve CD8 T cells. While cDC1 therapy has been highly effective in controlling primary and metastatic tumors,1–3 the mechanisms by which this treatment lead to effective tumor control remain unclear.Methods cDC1s for cancer therapy are generated from primary murine bone marrow ex vivo, purified, and stimulated in the presence of tumor antigen(s) prior to administration in vivo.1–3 To address whether the anti-tumor efficacy of cDC1 therapy requires migration to tdLNs, we compared the ability of wild type (WT) and Ccr7 -/- cDC1s to control melanoma tumor growth in vivo. We also asked whether our cDC1 therapy has the potential to elicit antigen spread, which is defined as induction and expansion of T cell responses that were not targeted by the initial therapy. To test this, we injected cDC1s loaded with ovalbumin (OVA) into OVA-expressing tumors and assessed the ability to control both OVA-positive and OVA-negative tumors in the primary and rechallenge settings.Results Our results suggest that Ccr7 -/- cDC1s delivered intratumorally are initially capable of inducing tumor control, yet prolonged tumor control requires CCR7-sufficient cDC1s. Moreover, in the context of aCTLA-4 ICB, both WT and Ccr7 -/- cDC1s significantly controlled tumor growth and prolonged mouse survival compared to any singular treatment. Additionally, we found that mice in which tumors were treated with cDC1s loaded with OVA could reject rechallenge with OVA-negative tumors. While this was observed in the presence and absence of aCTLA-4 ICB, combination treatment demonstrated greater efficacy of tumor control. We also found that mice treated with OVA-loaded cDC1s in the presence of aCTLA-4 ICB controlled bilateral OVA-positive and OVA-negative tumors.Conclusions In sum, our data suggest that cDC1 therapy can elicit key anti-tumor responses within the tumor microenvironment without migration to tdLNs and can generate diverse anti-tumor CD8 T cell responses, beyond those stimulated via antigens presented by the cDC1s used in treatment, particularly when combined with aCTLA-4 ICB. Overall, these findings suggest that cDC1s could be an effective cell therapy in the clinic and may provide further opportunities to improve tumor control.References Zhou Y, Slone N, Chrisikos TT, Kyrysyuk O, Babcock RL, Medik YB, Li HS, Kleinerman ES, Watowich SS. Vaccine efficacy against primary and metastatic cancer with in vitro-generated CD103 + conventional dendritic cells. JITC. 2020;8(1):1-13.Chrisikos TT, Zhou Y, Li HS, Babcock RL, Wan X, Patel B, Newton K, Mancuso JJ, Watowich SS. STAT3 Inhibits CD103+ cDC1 vaccine efficacy in murine breast cancer. Cancers 2020;12(1):1-16.Mahadevan KK, Dyevoich AM, Chen Y, Li B, Sugimoto H, Sockwell AM, McAndrews KM, Sthanam LK, Wang H, Shalapour S, Watowich SS, Kalluri R. Type I conventional dendritic cells facilitate immunotherapy in pancreatic cancer. Science 2024;384(6703):1-18.",
  "authors": [
    {
      "affiliations": [
        "The University of Texas MD Anderson Cancer Center, Houston, TX, USA"
      ],
      "name": "Morgan Riba"
    },
    {
      "affiliations": [
        "The University of Texas MD Anderson Cancer Center, Houston, TX, USA"
      ],
      "name": "Ariel P Nash"
    },
    {
      "affiliations": [
        "The University of Texas MD Anderson Cancer Center, Houston, TX, USA"
      ],
      "name": "Yifan Zhou"
    },
    {
      "affiliations": [
        "The University of Texas MD Anderson Cancer Center, Houston, TX, USA"
      ],
      "name": "Sunita Keshari"
    },
    {
      "affiliations": [
        "The University of Texas MD Anderson Cancer Center, Houston, TX, USA"
      ],
      "name": "Josue E Pineda"
    },
    {
      "affiliations": [
        "The University of Texas MD Anderson Cancer Center, Houston, TX, USA"
      ],
      "name": "Bhakti Patel"
    },
    {
      "affiliations": [
        "The University of Texas MD Anderson Cancer Center, Houston, TX, USA"
      ],
      "name": "Sarah Schneider"
    },
    {
      "affiliations": [
        "The University of Texas MD Anderson Cancer Center, Houston, TX, USA"
      ],
      "name": "Matthew M Gubin"
    },
    {
      "affiliations": [
        "The University of Texas MD Anderson Cancer Center, Houston, TX, USA"
      ],
      "name": "Stephanie S Watowich"
    }
  ],
  "title": "767 Type 1 conventional dendritic cell therapy coordinates tumor control in murine melanoma",
  "uid": "e60212a8-2994-59cd-a085-010fb2080426"
}