{
  "abstract": "Background Colon cancer (CC) remains a major cause of cancer-related mortality. Although immunotherapy has demonstrated efficacy in a subset of patients, outcomes vary widely, highlighting the need for predictive biomarkers and novel immunomodulatory targets to develop more effective therapeutic strategies.Methods A prospective cohort of 39 treatment-naïve colon cancer (CC) patients (27 stage III, 12 stage IV) was stratified according to clinical outcome into disease-free (DF, n=30) and disease recurrence (DR, n=9) groups. Baseline plasma levels of 32 soluble immune mediators were quantified and analyzed longitudinally across treatment time points, including pre-surgery, post-surgery, pre-chemotherapy, post-chemotherapy. Single-cell RNA sequencing (scRNA-seq) was performed using the BD Rhapsody system on tumor-infiltrating immune cells from baseline tumor specimens (n=6, collected prior to surgery), followed by analyses of immune cell composition, differential gene expressions, and pathway enrichment.Results Principal component and hierarchical clustering analyses of baseline plasma analytes did not segregate patients by clinical variables or outcome. However, IL-1α and IL-10 levels were significantly elevated in DR patients, and their combined profile predicted recurrence with an AUC of 0.84. Longitudinal cytokine network analysis revealed robust, coordinated Th1/lymphoid-associated interactions in DF patients, particularly involving IFNγ and TNFβ, persisting post-surgery. In contrast, DR patients exhibited fragmented networks driven by innate inflammatory mediators. Tumor scRNA-seq analyses showed enrichment of central memory CD4 + T cells and memory B cells in DF tumors, whereas DR samples presented higher monocyte infiltration, decreased B cell abundance, and elevated FOXP3+IL-17A+ regulatory T cells. DF tumors exhibited enriched pathways related to antigen processing and T cell activation, while DR tumors were characterized by IL-1 signaling and Th17-associated transcripts, consistent with immune dysregulation.Conclusions Baseline elevations of IL-1α and IL-10 and innate-skewed cytokine networks were associated with recurrence in CC patients. In contrast, DF patients displayed Th1/lymphoid signatures and a coordinated systemic immune response. These findings highlight the prognostic utility of immune profiling and suggest therapeutic value in targeting regulatory and inflammatory axes in high-risk patients.Acknowledgements Supported by FAPESP (grant numbers #21/00408-6; 2024/10964-1), GSK, and Trust in Science.Ethics Approval This study was conducted in accordance with the Declaration of Helsinki and approved by the Research Ethics Committee of the Hospital Israelita Albert Einstein (CAAE: 54281321.6.0000.0071; Approval Number: 6.821.782).",
  "authors": [
    {
      "affiliations": [
        "Hospital Israelita Albert Einstein, São Paulo, São Paulo, Brazil"
      ],
      "name": "João F Scarini"
    },
    {
      "affiliations": [
        "Hospital Israelita Albert Einstein, São Paulo, São Paulo, Brazil"
      ],
      "name": "Amanda B Figueiredo"
    },
    {
      "affiliations": [
        "Hospital Israelita Albert Einstein, São Paulo, São Paulo, Brazil"
      ],
      "name": "Juliana S Apostolico"
    },
    {
      "affiliations": [
        "Hospital Israelita Albert Einstein, São Paulo, São Paulo, Brazil"
      ],
      "name": "Luiz Gustavo F Cortes"
    },
    {
      "affiliations": [
        "Hospital Israelita Albert Einstein, São Paulo, São Paulo, Brazil"
      ],
      "name": "Lukas Iohan"
    },
    {
      "affiliations": [
        "Hospital Israelita Albert Einstein, São Paulo, São Paulo, Brazil"
      ],
      "name": "Iara M Messias"
    },
    {
      "affiliations": [
        "Hospital Israelita Albert Einstein, São Paulo, São Paulo, Brazil"
      ],
      "name": "Joselany S Baroni"
    },
    {
      "affiliations": [
        "Hospital Israelita Albert Einstein, São Paulo, São Paulo, Brazil"
      ],
      "name": "Kátia LP Morais"
    },
    {
      "affiliations": [
        "Hospital Israelita Albert Einstein, São Paulo, São Paulo, Brazil"
      ],
      "name": "Thaís Romano"
    },
    {
      "affiliations": [
        "Hospital Israelita Albert Einstein, São Paulo, São Paulo, Brazil"
      ],
      "name": "Pedro LS Usón Junior"
    },
    {
      "affiliations": [
        "Hospital Israelita Albert Einstein, São Paulo, São Paulo, Brazil"
      ],
      "name": "Fernando Moura"
    },
    {
      "affiliations": [
        "Hospital Municipal Vila Santa Catarina, São Paulo, São Paulo, Brazil"
      ],
      "name": "Victor E Seid"
    },
    {
      "affiliations": [
        "Hospital Israelita Albert Einstein, São Paulo, São Paulo, Brazil"
      ],
      "name": "Karla Pelegrino"
    },
    {
      "affiliations": [
        "Hospital Israelita Albert Einstein, São Paulo, São Paulo, Brazil"
      ],
      "name": "Matheus Martinelli"
    },
    {
      "affiliations": [
        "Hospital Israelita Albert Einstein, São Paulo, São Paulo, Brazil"
      ],
      "name": "Paulo V Campregher"
    },
    {
      "affiliations": [
        "Hospital Israelita Albert Einstein, São Paulo, São Paulo, Brazil"
      ],
      "name": "Tatiana F Almeida"
    },
    {
      "affiliations": [
        "Hospital Municipal Vila Santa Catarina, São Paulo, São Paulo, Brazil"
      ],
      "name": "Thiago Trolez Amancio"
    },
    {
      "affiliations": [
        "Hospital Israelita Albert Einstein, São Paulo, São Paulo, Brazil"
      ],
      "name": "Renée Z Filippi"
    },
    {
      "affiliations": [
        "Hospital Israelita Albert Einstein, São Paulo, São Paulo, Brazil"
      ],
      "name": "Kenneth J Gollob"
    }
  ],
  "title": "42 Baseline systemic immune mediators and tumor microenvironment features associated with disease outcomes in colon cancer",
  "uid": "774deb29-9e87-5e39-841e-c23a4bbc1822"
}