{
  "abstract": "Background The advent of immune checkpoint inhibitors (ICIs), anti-PD-1/anti-PD-L1 antibodies, has markedly improved treatment response and overall survival rates in non-small cell lung cancer (NSCLC). However, only 15-40% of patients benefit from ICIs therapy. Therefore, identification of biomarkers associated with responses are mandated in order to increase the efficacy of such therapy. The primary objective of the study aimed to identify pre- and post-treatment immune modulatory cytokines and immune checkpoint molecules levels as predictors of response to anti-PD-1/PD-L1 therapy in NSCLC patients.Methods The study was conducted at the National Center for Cancer Care and Research, Hamad Medical Corporation, Qatar from September 2021-June 2023. Sera from 31 locally advanced/metastatic NSCLC patients, eligible for anti-PD-1/PD-L1 or combined chemoimmunotherapy, was collected pre- and post-treatment. A total of 65 Soluble immune modulatory cytokines and 72 immune checkpoint molecules were tested using Procarta Plex kits. The differential expression of the soluble markers was analyzed using Wilcoxon Signed Rank test and Mann-Whitney U test. Treatment response was assessed via PET-CT imaging and clinical assessment per RECIST criteria.Results In non-responders, T cell immune inhibitory checkpoints, PD-1, CD276 were significantly up-regulated after treatment. Furthermore, the elevated soluble CD134 and CD137 levels observed in non-responder may contribute to T cell function impairment. Additionally, natural killer cells inhibitory markers Arginase-1 and Nectin-2 were also found to be significantly upregulated in non-responders after treatment.Analysis of circulating immuno-oncology cytokines demonstrated that the upregulation of IL-15, IL-10, IL-2, IL-20, IL-21 and MCSF was associated with a favorable response while the upregulation of MIP1 alpha, MIP3 alpha, MIP1 beta, SDF1 alpha, TNF alpha, TNF receptor, TRAIL and TWEAK could imply an impaired response to ICIs +/- chemotherapy in NSCLC. These findings demonstrate the crucial role of these mediators in driving treatment response to ICIs.Analysis of soluble mediators with TPD-L1 status showed a significant upregulation of soluble immune inhibitory CD276 and CD134 in TPD-L1 positive non-responders while in TPD-L1 negative non-responders, significant downregulation of soluble CD134 and CD28 was observed post-treatment. Similarly, in non-responding patients with more than 50% TPD-L1status, significant upregulation of soluble CD134 was observed after treatment. The results shows high TPD-L1 expression could be associated with an upregulation of the soluble immune inhibitory markers CD274 and CD134 leading a poor outcome.Conclusions These results can serve as baseline data for conducting larger studies in NSCLC to understand the role of identified soluble mediators as non-invasive prognostic and predictive biomarkers.Ethics Approval Study has obtained ethic approval",
  "authors": [
    {
      "affiliations": [
        "Translational Research Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar"
      ],
      "name": "Kirti S Prabhu"
    },
    {
      "affiliations": [
        "Hamad Bin Khalifa University, Doha, Qatar"
      ],
      "name": "Sarra Mestiri"
    },
    {
      "affiliations": [
        "Department of Biomedical Sciences, College of Health Sciences, Abu Dhabi University, Abu Dhabi, United Arab Emirates"
      ],
      "name": "Afsheen Raza"
    },
    {
      "affiliations": [
        "Translational Cancer Research Facility, Translational Research Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar"
      ],
      "name": "Varghese Philipose Inchakalody"
    },
    {
      "affiliations": [
        "Department of Medical Oncology, National Center for Cancer Care and Research, Hamad Medical Corporation, Doha, Qatar"
      ],
      "name": "Reyad Mohsen"
    },
    {
      "affiliations": [
        "Department of Medical Oncology, National Center for Cancer Care and Research, Hamad Medical Corporation, Doha, Qatar"
      ],
      "name": "Aladin Kanbour"
    },
    {
      "affiliations": [
        "Department of Medical Oncology, National Center for Cancer Care and Research, Hamad Medical Corporation, Doha, Qatar"
      ],
      "name": "Abdul Rehman Zar Gul"
    },
    {
      "affiliations": [
        "Department of Medical Oncology, National Center for Cancer Care and Research, Hamad Medical Corporation, Doha, Qatar"
      ],
      "name": "Anite Philip"
    },
    {
      "affiliations": [
        "Department of Medical Oncology, National Center for Cancer Care and Research, Hamad Medical Corporation, Doha, Qatar"
      ],
      "name": "Suma Vijayakumar"
    },
    {
      "affiliations": [
        "Weill Cornell Medicine College, Doha Qatar"
      ],
      "name": "Shereena Hydrose"
    },
    {
      "affiliations": [
        "Diagnostic Genomic Division, Department of Laboratory Medicine and Pathology, Hamad Medical Corporation, Doha, Qatar"
      ],
      "name": "Wafa Abualainin"
    },
    {
      "affiliations": [
        "Translational Research Institute and Dermatology Institute, Academic Health System, Hamad, Medical Corporation, Doha, Qatar"
      ],
      "name": "Shahab Uddin Khan"
    },
    {
      "affiliations": [
        "Translational Oncology Research Center, Qatar Biomedical Research Institute, Doha, Qatar"
      ],
      "name": "Fares Al- Ejeh"
    },
    {
      "affiliations": [
        "Department of Medical Oncology, National Center for Cancer Care and Research, Hamad Medical Corporation, Doha, Qatar"
      ],
      "name": "Ussama Al Homsi"
    },
    {
      "affiliations": [
        "National Center for Cancer Care and Research NCCCR, Doha, Qatar"
      ],
      "name": "Said Dermime"
    }
  ],
  "title": "627 Soluble immune modulatory cytokines and immune checkpoint molecules as predictors of response to anti-PD-1/PD-L1 therapy in non-small cell lung cancer patients",
  "uid": "dd46a424-2aee-545a-a5c2-bc08a0abd702"
}