{
  "abstract": "Background Immune checkpoint inhibitor (ICI) therapies have revolutionized oncology, but identifying patients who benefit remains a challenge, particularly in populations where ICIs are not the standard of care, including microsatellite stable colorectal cancer (MSS CRC) and rare solid cancers. We evaluated real-world performance of the Immune Profile Score (IPS), a validated DNA- and RNA-based molecular signature, in these cohorts. Methods In an exploratory analysis, we analyzed two real-world cohorts: 1) MSS CRC; and 2) MSS, tumor mutational burden-low rare solid cancers treated with off-label ICI. IPS-High and IPS-Low were calculated using a previously validated threshold. Cox proportional hazards models were fit to demonstrate prognostic utility for real-world overall survival (rwOS). In MSS CRC, time-to-next-treatment (TTNT) on prior non-ICI therapy was compared to rwOS on subsequent ICI therapy. Results In MSS CRC (n=46), IPS-High patients (13%) demonstrated clinically meaningful improvement in rwOS versus IPS-Low (Median OS: not reached vs 7.3 months; HR = 0.22, 90% CI 0.04-1.16). While IPS was not associated with TTNT on the preceding non-ICI line (HR = 1.07, 90% CI 0.60-1.91), it was associated with OS in patients receiving later line ICI (HR 0.21, 90% CI 0.04-1.22). In the rare cancers cohort (n=90; 26 unique malignancies), IPS-High (17.8%) was associated with longer OS to ICI therapy (HR = 0.26, 90% CI 0.11-0.61), even when restricted to histologies represented in both IPS groups (HR = 0.18, 90%, CI 0.05-0.62). Conclusions Preliminary evidence suggests that IPS may serve as a generalizable, pan-cancer biomarker capable of stratifying outcomes for ICI treatment in populations traditionally excluded from immunotherapy benefit.",
  "abstract_shown": true,
  "affiliations": [
    "Tempus AI, Inc., Chicago, IL"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 26,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "M. A. Ting-Lin"
    },
    {
      "name": "E. S. Antonarakis"
    },
    {
      "name": "X. Wang"
    },
    {
      "name": "R. Erbe"
    },
    {
      "name": "A. D. Zander"
    },
    {
      "name": "Y. Liu"
    },
    {
      "name": "A. Jin"
    },
    {
      "name": "G. A. Vidal"
    },
    {
      "name": "S. M. Haake"
    },
    {
      "name": "M. M. Stein"
    },
    {
      "name": "D. F. DeSantis"
    },
    {
      "name": "K. A. Beauchamp"
    },
    {
      "name": "M. E. Campbell"
    },
    {
      "name": "E. E. W. Cohen"
    },
    {
      "name": "S. W. Hyun"
    },
    {
      "name": "R. J. Kelly"
    },
    {
      "name": "A. Kalyan"
    },
    {
      "name": "B. Bashir"
    },
    {
      "name": "B. J. Rimel"
    },
    {
      "name": "T. J. Herzog"
    },
    {
      "name": "V. L. Chiou"
    },
    {
      "name": "C. Sangli"
    },
    {
      "name": "H. Nimeiri"
    },
    {
      "name": "J. Carlson"
    },
    {
      "name": "D. M. Simeone"
    },
    {
      "name": "J. H. Strickler"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5csnsy7rnng5x.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.07.26364989",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.10.07.26364989v1.full",
  "id": "5csnsy7rnng5x",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.10.07.26364989v1",
  "language": null,
  "licence": "PDM-1.0",
  "licence_label": "Public domain",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/publicdomain/mark/1.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "medrxiv",
      "oncology"
    ],
    [
      "openalex",
      "2730|Cancer Immunotherapy and Biomarkers"
    ]
  ],
  "openalex": "W7221115681",
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.10.07.26364989v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-07",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/5csnsy7rnng5x.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:34Z",
      "native_id": "10.64898/2026.10.07.26364989",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.10.07.26364989v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "medrxiv:oncology",
      "subfield": "oncology"
    }
  ],
  "title": "Multimodal Immune Profile Score (IPS) as a Pan-Cancer Biomarker for Stratifying Outcomes of Immune Checkpoint Inhibitor Benefit in Microsatellite Stable Colorectal Cancer and Rare Solid Tumors",
  "title_text": "Multimodal Immune Profile Score (IPS) as a Pan-Cancer Biomarker for Stratifying Outcomes of Immune Checkpoint Inhibitor Benefit in Microsatellite Stable Colorectal Cancer and Rare Solid Tumors",
  "type": "preprint",
  "updated_at": "2026-10-30T12:20:34Z",
  "url": "https://research.draconitic.com/paper/5csnsy7rnng5x",
  "venue": "medRxiv",
  "versions": []
}