{
  "abstract": "Background Triple-negative breast cancer (TNBC) is an aggressive subtype, comprising 10-15% of breast cancers. Immune checkpoint inhibitors (ICIs), especially when combined with radiation therapy (RT), have shown promise, and tumor microenvironment (TME) immune cell presence correlates with ICI response. While distinct TME immune phenotypes (R1, R2, and non-responders) have been characterized, the overarching contribution of systemic immunity to these diverse treatment responses is not fully understood. By investigating the role of these broader immune components in treatment outcomes, this study aims to identify accurate predictive biomarkers.Methods We collected baseline and on treatment PBMC samples (n=54) from patients enrolled in NCT03366844, and performed single cell RNA sequencing(scRNAseq), single cell TCR/BCR sequencing (scTCR/BCR seq) and CITE sequencing on CD45+ cells, which was combined with tumor data of each patient.Results By analyzing the scRNA and scTCR/BCR data and by tracking each clonotype, we discovered that T cells in PBMCs provides a reflection of ongoing tumor responses (1018 clonotypes). We observed that with treatment, a PBMC enriched cell type Temra CD8 T was key contributor of systemic immunity as they were able to transition to clinically relevant CD8 T cells in the tumor and contribute to response. Interestingly these systemic immune responses were different between the response groups i.e. In R1 responders we observed that the response was driven by T cells in local TME, whereas in R2 responders the response was derived from Temra CD8. Our investigation also uncovered metabolic differences in Temra CD8 T cells from R2 responders compared to non-responders.Conclusions Importantly, by integrating analyses of both tumor and peripheral blood mononuclear cells (PBMCs), we were able to detect systemic immunity within PBMCs at baseline and were able to discover the involvement of Temra T cells in the differentiation process of tumor-reactive T cells. This latter finding is particularly significant as R2 responders are characterized by an immune-excluded phenotype, suggesting a more complex interplay of systemic immunity than previously assumed.",
  "authors": [
    {
      "affiliations": [
        "Cedars Sinai Medical Center, Los Angeles, CA, USA"
      ],
      "name": "Vaishnavi Devarakonda"
    },
    {
      "affiliations": [
        "Cedars Sinai Medical Center, Los Angeles, CA, USA"
      ],
      "name": "Stephen L Shiao"
    },
    {
      "affiliations": [
        "Emory University, Atlanta, GA, USA"
      ],
      "name": "Elvin Canseco"
    },
    {
      "affiliations": [
        "Cedars Sinai Medical Center, Los Angeles, CA, USA"
      ],
      "name": "Na Jeong Kim"
    },
    {
      "affiliations": [
        "Cedars Sinai Medical Center, Los Angeles, CA, USA"
      ],
      "name": "Anthony T Nguyen"
    },
    {
      "affiliations": [
        "Cedars Sinai Medical Center, Los Angeles, CA, USA"
      ],
      "name": "Jolene Viramontes"
    }
  ],
  "title": "669 Characterization of matched tumor and peripheral blood revealed temra T cells play a central role in eliciting systemic immune responses in TNBC patients treated with anti-PD1 and radiation",
  "uid": "81a46833-2ec5-5ef1-af87-05bb374aee40"
}