{
  "abstract": "The immunomodulatory effects of chemotherapy (chemoimmunomodulation; CIM) are clinically consequential and heterogeneous, yet no systematic framework exists for classifying the immunomodulatory trajectory a tumor follows in response to treatment (CIM trajectory). Here, we present the CIM Induction Classifier (CIMIC), an unsupervised clustering pipeline leveraging delta gene expression across 3,189 CIM-related genes to classify specimens chemoimmunomodulatory trajectory. Applied to two pre- and post-chemotherapy breast cancer (BC) datasets (NKI/SMC, N = 36; NEO, N = 19) and nine epirubicin-perturbed triple-negative BC (TNBC) cell lines, CIMIC identified two divergent CIM trajectories: a functional CIM (Fun-CIM) trajectory, broadly conserved across tumors and cell lines and characterized by induction of inflammatory cell death, antigen presentation, viral mimicry, and adaptive immune activation programs, and a dysfunctional CIM (Dys-CIM) trajectory, characterized by induction of proteostatic and metabolic stress-adaptation programs, reduced immune cell abundances and cytotoxic activity, and enrichment of aggressive BC subtypes. Using survival and longitudinal transcriptomic data in NKI/SMC (N = 20), treatment-induced increases in Fun-CIM-associated genes and ssGSEA scores were associated with reduced recurrence, whereas Dys-CIM-associated genes and scores were associated with increased recurrence. In multivariable analyses within independent chemotherapy-treated BC cohorts (METABRIC, N = 412; SCAN-B, N = 2,462), higher baseline Fun-CIM ssGSEA scores were associated with better outcomes, whereas higher baseline Dys-CIM ssGSEA scores were associated with worse outcomes. These findings establish CIM as a dynamic, trajectory-level process and position CIMIC as a framework for defining CIM trajectories and supporting future efforts to identify predictors, mechanisms, and therapeutic strategies that maximize beneficial CIM.",
  "abstract_shown": true,
  "affiliations": [
    "University of Florida"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "name": "I. Lopes de Lima"
    },
    {
      "name": "E. Molchan"
    },
    {
      "name": "K. H. Streeks"
    },
    {
      "name": "K. L. Coleman"
    },
    {
      "name": "M. S. Makarem"
    },
    {
      "name": "N. Seligson"
    },
    {
      "affs": [
        0
      ],
      "name": "M. O. Gbadamosi"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1m73w0dwmy98x.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.24.754178",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.24.754178v1.full",
  "id": "1m73w0dwmy98x",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.24.754178v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "cancer biology"
    ],
    [
      "openalex",
      "1306|Breast Cancer Treatment Studies"
    ]
  ],
  "openalex": "W7214658190",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.24.754178v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-24",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/1m73w0dwmy98x.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:24:48Z",
      "native_id": "10.64898/2026.09.24.754178",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.24.754178v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:cancer biology",
      "subfield": "oncology"
    }
  ],
  "title": "Unsupervised transcriptomic analysis of paired pre- and post-treatment specimens reveals divergent chemoimmunomodulatory induction trajectories in breast cancer",
  "title_text": "Unsupervised transcriptomic analysis of paired pre- and post-treatment specimens reveals divergent chemoimmunomodulatory induction trajectories in breast cancer",
  "type": "preprint",
  "updated_at": "2026-10-30T12:24:48Z",
  "url": "https://research.draconitic.com/paper/1m73w0dwmy98x",
  "venue": "bioRxiv",
  "versions": []
}