{
  "abstract": "Background Metastatic Breast Cancer (MBC) poses a significant clinical challenge where immunotherapies targeting the PD-1/PD-L1 axis have had limited success in contrast to early breast cancer (EBC) where there may be greater immune competence and lower tumour burden.Methods Here we conducted a complementary multi-platform immune profiling study to define differences in the immune landscapes of 191 breast cancer (BC) patients to uncover the mechanisms behind immune escape leading to a loss of immune surveillance. High-dimensional single-cell flow cytometry revealed distinct immune profiles between early and metastatic disease.Results MBC was associated with features of chronic systemic inflammation and immune exhaustion, including suppressed Th1 responses, increased expression of activation markers (CD86, HLA-DR, and NKG2D) on T cells, and an enrichment of terminally exhausted (PD-1 + TIM-3+) T cells. Conversely, EBC patients showed heightened immune activation upon in vitro stimulation, as evidenced by elevated NKG2D expression on isolated NK cells and CD38 expression on isolated CD8+ T cells. Additionally, profiling of the NKG2D-NKG2DL axis on circulating tumour cells (CTCs) show expression of the ligands in early and advanced disease. Further stratification within the MBC cohort revealed immune heterogeneity correlating with treatment response and survival. Notably, exceptional survivors of metastatic disease exhibited lower TIM3 expression on peripheral effector subsets, both ex vivo and upon in vitro activation, and a reduction in short-lived, CD86-expressing plasmablasts compared to rapid progressors.Conclusions These findings highlight discrete immune phenotypes in MBC that may contribute to the attenuated efficacy of current immunotherapeutic strategies.",
  "authors": [
    {
      "affiliations": [
        "King’s College London, London, UK"
      ],
      "name": "Helen Kakkassery"
    },
    {
      "affiliations": [
        "King’s College London, London, UK"
      ],
      "name": "Paul R Buckley"
    },
    {
      "affiliations": [
        "King’s College London, London, UK"
      ],
      "name": "Thanussuyah Alaguthurai"
    },
    {
      "affiliations": [
        "&Lstrok",
        "ukasiewicz Research Network – PORT Polish Center for Technology Development, Wroclaw, Poland"
      ],
      "name": "Patrycja Gazińska"
    },
    {
      "affiliations": [
        "King’s College London, London, UK"
      ],
      "name": "Rosalind Graham"
    },
    {
      "affiliations": [
        "Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, London, UK"
      ],
      "name": "Ruifang Lu"
    },
    {
      "affiliations": [
        "King’s College London, London, UK"
      ],
      "name": "Esme Carpenter"
    },
    {
      "affiliations": [
        "The Institute of Cancer Research, London, UK"
      ],
      "name": "Zuzanna Kozik"
    },
    {
      "affiliations": [
        "Guy’s and St Thomas’ Hospital NHS Foundation Trust, London, UK"
      ],
      "name": "Farhana Hossain"
    },
    {
      "affiliations": [
        "The Institute of Cancer Research, London, UK"
      ],
      "name": "Jyoti Choudhary"
    },
    {
      "affiliations": [
        "King’s College London, London, UK"
      ],
      "name": "Sheeba Irshad"
    }
  ],
  "title": "772 Distinct immune signatures in early and metastatic breast cancer define mechanisms of immune escape and identify immune correlates of exceptional survival in stage IV disease",
  "uid": "6d558485-211e-55b5-9232-6383cbed2103"
}