{
  "abstract": "Background Perioperative immune checkpoint inhibition is emerging as a promising strategy for high-risk, resectable cutaneous squamous cell carcinoma (CSCC). However, biomarkers capable of predicting pathological response and recurrence remain undefined. We report clinical and translational findings from NEO-CESQ (NCT04632433), a multicenter, single-arm phase II trial evaluating neoadjuvant plus adjuvant cemiplimab in patients with stage III–IV resectable CSCC.Methods Patients received neoadjuvant cemiplimab followed by surgery and adjuvant treatment. The primary endpoint was major pathological response (MPR; <10% viable tumor) assessed in the intention-to-treat population. Survival outcomes were estimated using HRs with 95% CIs. Exploratory translational analyses included baseline tumor transcriptomics (NanoString PanCancer IO 360) and longitudinal serum cytokine profiling. Differential expression and signature enrichment analyses were performed to identify molecular correlates of response. An exploratory transcriptional classifier associated with recurrence-free survival was developed, and its performance was evaluated using the area under the curve (AUC).Results MPR was achieved in 11 of 25 patients (44%), while pathological complete response (pCR) occurred in nine patients (36%). With a median follow-up of 42 months, MPR was associated with improved event-free survival (HR 0.16, 95% CI 0.03–0.75), although recurrence events were limited. Patients achieving pCR exhibited lower circulating interleukin 6 (IL-6) levels prior to adjuvant therapy compared with non-pCR patients, but IL-6 did not significantly discriminate MPR status or survival outcomes. Tumor transcriptomic analyses revealed enrichment of interferon-γ-related signatures in responders, whereas non-responders showed higher expression of WNT5A and CD276. An exploratory 10-gene classifier (“NeoSquamos”) demonstrated an AUC of 0.838 for recurrence-free survival prediction, though based on a limited number of events.Conclusions These findings provide an integrated view of tumor and systemic immune dynamics during perioperative programmed death 1 blockade in CSCC. Candidate biomarkers, including transcriptomic signatures and circulating cytokines, may help refine risk stratification, although prospective validation in larger cohorts is required.Trial registration number NCT04632433.",
  "abstract_shown": true,
  "affiliations": [
    "Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie, Universitatsklinikum Essen, Essen, Germany",
    "Epidemiology and Biostatistics, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy",
    "Dermatology, University of Duisburg-Essen, Essen, Germany",
    "Melanoma and Skin Cancers Surgery Unit, Istituto Nazionale Tumori IRCCS Fondazione “G. Pascale”, Naples, Italy",
    "Melanoma, Cancer Immunotherapy and Development Therapeutics, Istituto Nazionale Tumori IRCCS Fondazione Pascale, Naples, Italy",
    "Dipartimento di Neuroscienze e Scienze Riproduttive ed Odontostomatologiche, Università degli Studi di Napoli “Federico II“, Naples, Italy",
    "Veneto Institute of Oncology IOV IRCCS, Padova, Italy",
    "Division of Medical Oncology for Melanoma, Sarcoma and Rare Tumors, European Institute of Oncology IRCCS, Milan, Italy",
    "Medicine and Surgery, University of Perugia, Perugia, Italy",
    "University of Florence, Florence, Italy",
    "Plastic Surgery Clinic, Padua University Hospital, Padua, Italy",
    "Humanitas University, Milan, Italy",
    "Melanoma and Sarcoma Surgery, European Institute of Oncology IRCCS, Milan, Italy",
    "IRCCS Ospedale Policlinico San Martino, Genoa, Italy",
    "Department of Medical and Surgical Specialties, University of Brescia, Brescia, Italy",
    "Maxillofacial Surgery Unit, Perugia, Italy",
    "Clinical Research Technology S.r.l. (CRT), Salerno, Italy"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 20,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Dirk Schadendorf"
    },
    {
      "affs": [
        1
      ],
      "name": "Diana Giannarelli"
    },
    {
      "affs": [
        2
      ],
      "name": "Elisabeth Livingstone"
    },
    {
      "affs": [
        3
      ],
      "name": "Corrado Caracò"
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    {
      "affs": [
        4
      ],
      "name": "Miriam Paone"
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    {
      "affs": [
        4
      ],
      "name": "Domenico Mallardo"
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    {
      "affs": [
        5
      ],
      "name": "Paolo A Ascierto"
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    {
      "affs": [
        6
      ],
      "name": "Luisa Piccin"
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    {
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        7
      ],
      "name": "Paola Queirolo"
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    {
      "affs": [
        4
      ],
      "name": "Claudia Trojaniello"
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    {
      "affs": [
        8
      ],
      "name": "Mario Mandala"
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    {
      "affs": [
        9
      ],
      "name": "Daniela Massi"
    },
    {
      "affs": [
        10
      ],
      "name": "Franco Bassetto"
    },
    {
      "affs": [
        11
      ],
      "name": "Paolo Bossi"
    },
    {
      "affs": [
        12
      ],
      "name": "Elisabetta Pennacchioli"
    },
    {
      "affs": [
        13
      ],
      "name": "Francesco Spagnolo"
    },
    {
      "affs": [
        14
      ],
      "name": "Vittorio Rampinelli"
    },
    {
      "affs": [
        15
      ],
      "name": "Francesco Giovacchini"
    },
    {
      "affs": [
        16
      ],
      "name": "Paola Schiavo"
    },
    {
      "affs": [
        13
      ],
      "name": "Giampiero Parrinello"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0yg0ebqw2z2qw.bib",
  "cited_by": 0,
  "doi": "10.1136/jitc-2026-016059",
  "fulltext_url": "https://jitc.bmj.com/content/14/11/e016059.full",
  "id": "0yg0ebqw2z2qw",
  "issns": [
    "2051-1426"
  ],
  "landing_url": "https://doi.org/10.1136/jitc-2026-016059",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "RC254-282"
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    [
      "openalex",
      "2708|Nonmelanoma Skin Cancer Studies"
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  "pdf_url": "https://jitc.bmj.com/content/14/11/e016059.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-08",
  "publisher": "BMJ Publishing Group",
  "ris": "https://research.draconitic.com/paper/0yg0ebqw2z2qw.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T14:21:26Z",
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  "subjects": [
    {
      "field": "biology",
      "origin": "journal-openalex:2403|Immunotherapy and Immune Responses",
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    {
      "field": "medicine",
      "origin": "lcc:RC254-282",
      "subfield": "oncology"
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  ],
  "title": "Integrated tumor and circulating immune profiling in the NEO-CESQ trial of perioperative cemiplimab for resectable cutaneous squamous cell carcinoma",
  "title_text": "Integrated tumor and circulating immune profiling in the NEO-CESQ trial of perioperative cemiplimab for resectable cutaneous squamous cell carcinoma",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T14:21:26Z",
  "url": "https://research.draconitic.com/paper/0yg0ebqw2z2qw",
  "venue": "Journal for ImmunoTherapy of Cancer",
  "versions": []
}