{
  "abstract": "Background Immune checkpoint blockade (ICB) therapy has shown promise for treating head and neck squamous cell carcinoma (HNSCC), but only a subset of patients exhibit a meaningful response. Hence, identifying predictive biomarkers of the ICB response remains a critical roadblock.Methods Here, for the first time, we systematically characterize the dynamic changes in the blood during ICB treatment across four different time points in a mouse HNSCC model treated with anti-PD-1 ICB. We profile serial pre and on-treatment liquid biopsies, both by single cell (SC) and bulk RNA with tandem SC-TCR sequencing to identify liquid predictors of the ICB response.Results This study charts the host peripheral response to ICB therapy on an unprecedented scale. We observe significant differences in the clonal expansion and temporal dynamics of effector memory T cells (Tem) and B cells between responders and non-responder mice. These changes were most prominent in mice at an early on-treatment time point, highlighting this time point as optimal for assessing ICB efficacy. Remarkably, the resulting LiBIO score which integrates the Tem and B cell signatures, successfully predict ICB response in HNSCC patients across multiple tumor and blood cohorts, without any additional training. Its application using one fixed decision threshold yields a fairly high predictive odds ratio of response, which surpasses the predictive power of existing biomarkers, including a newly generated validation cohort of HNSCC patients treated with ICB ( figure 1).Conclusions Collectively, our preclinical insights support the premise that peripheral immune events can serve as a foundation for biomarker discovery, offering a non-invasive, biologically grounded approach to monitor and predict immunotherapy outcomes with high fidelity in HNSCC patients. Finally, the approach presented lays a solid basis for developing similar biomarkers in other cancer indications.Abstract 489 Figure 1",
  "authors": [
    {
      "affiliations": [
        "National Cancer Institute, National Institutes of Health, Bethesda, MD, USA"
      ],
      "name": "Binbin Wang"
    },
    {
      "affiliations": [
        "MD Anderson, La Jolla, CA, USA"
      ],
      "name": "Robert Saddawi-Konefka"
    },
    {
      "affiliations": [
        "NIH-NCI, Doha, Qatar"
      ],
      "name": "Kun Wang"
    },
    {
      "affiliations": [
        "Moores Cancer Center, La Jolla, CA, USA"
      ],
      "name": "Silvio Gutkind"
    },
    {
      "affiliations": [
        "National Cancer Institute, National Institutes of Health, Bethesda, MD, USA"
      ],
      "name": "Eytan Ruppin"
    }
  ],
  "title": "489 Longitudinal liquid biopsy identifies an early predictive biomarker of immune checkpoint blockade response in head and neck squamous cell carcinoma",
  "uid": "4b920959-f527-5e77-8cef-5ecb2fd8166c"
}