{
  "abstract": "Understanding how tumor cells shape the tumor microenvironment (TME) and evade the host immune response is critical for developing novel therapeutic combinations. In this study, we identify tumor cell p38α as a therapeutic target that restricts antitumor immunity and contributes to resistance against immune-checkpoint inhibitors (ICIs). Genetic analyses of mouse and human melanomas reveal alterations in the mitogen-activated protein kinase (MAPK)-stress pathway, including upregulation of MAPK14. We demonstrate a dual role for p38α in ultraviolet-B (UVB)-induced Braf V600E melanoma, acting as a tumor suppressor during melanocyte transformation but promoting melanoma growth and progression. Mechanistically, p38α impairs cytotoxic immune responses, modulates immunosuppressive myeloid cells, and regulates inflammatory mediators that shape the TME. Loss or inhibition of p38α enhances and restores sensitivity to PD-1 blockade, resulting in tumor regression and improved overall survival. Moreover, a p38α-associated gene signature correlates with favorable immunotherapy outcomes in patients with melanoma, underscoring its translational relevance.",
  "abstract_shown": true,
  "affiliations": [
    "Biomedical Research in Melanoma-Animal Models and Cancer Laboratory-Vall d´Hebron Research Institute VHIR-Vall d'Hebron Hospital-UAB, Instituto de Investigación Sanitaria Hospital Universitari Vall d'Hebron (IIS IR-HUVH), Barcelona, Spain.",
    "Centro Nacional de Análisis Genómico (CNAG), Barcelona, Spain.",
    "Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, Barcelona, Spain.",
    "Institució Catalana de Recerca i Estudis Avançats (ICREA), Passeig Lluís Companys 23, Barcelona, Spain.",
    "Animal Laboratory Unit; Biomedical Research Park of Barcelona-PRBB, Barcelona, Spain.",
    "Independent researcher, Madrid, Spain.",
    "University of Barcelona, Bellvitge, Spain.",
    "Neurology Department, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Vall d´Hebron Research Institute VHIR-Vall d'Hebron Hospital-UAB, Instituto de Investigación Sanitaria Hospital Universitari Vall d'Hebron (IIS IR-HUVH), Barcelona, 08035, Spain.",
    "Childhood Cancer and Blood Disorders Group, Vall d´Hebron Research Institute VHIR-Vall d'Hebron Hospital-UAB, Instituto de Investigación Sanitaria Hospital Universitari Vall d'Hebron (IIS IR-HUVH), Barcelona, 08035, Spain.",
    "Anatomy Pathology Department, Vall d'Hebron Hospital-UAB, Barcelona, Spain.",
    "Universitat de Barcelona, Barcelona, Spain.",
    "Vall d'Hebron Institute of Oncology VHIO-Vall d'Hebron Hospital-UAB, Instituto de Investigación Sanitaria Hospital Universitari Vall d'Hebron (IIS IR-HUVH), Barcelona, Spain.",
    "Dermatology Department, Vall d'Hebron Hospital-UAB, Barcelona, Spain.",
    "Biomedical Research in Melanoma-Animal Models and Cancer Laboratory-Vall d´Hebron Research Institute VHIR-Vall d'Hebron Hospital-UAB, Instituto de Investigación Sanitaria Hospital Universitari Vall d'Hebron (IIS IR-HUVH), Barcelona, Spain. juan.recio@vhir.org."
  ],
  "article_type": "research support, non u.s. gov't",
  "arxiv": null,
  "author_total": 18,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Paula Granado-Martínez",
      "orcid": "0000-0002-7765-8914"
    },
    {
      "affs": [
        0
      ],
      "name": "Kimberley McGrail",
      "orcid": "0000-0001-7227-7306"
    },
    {
      "affs": [
        0
      ],
      "name": "Roberto Orsenigo",
      "orcid": "0000-0003-4048-8605"
    },
    {
      "affs": [
        1
      ],
      "name": "Ginevra Caratù"
    },
    {
      "affs": [
        1
      ],
      "name": "Paula Nieto"
    },
    {
      "affs": [
        0
      ],
      "name": "Yuxin Ding"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Ángel Nebreda",
      "orcid": "0000-0002-7631-4060"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Juan Martín-Caballero"
    },
    {
      "affs": [
        4,
        6
      ],
      "name": "Iván Ortega"
    },
    {
      "affs": [
        7
      ],
      "name": "Herena Eixarch"
    },
    {
      "affs": [
        7
      ],
      "name": "Carmen Espejo",
      "orcid": "0000-0001-9949-5901"
    },
    {
      "affs": [
        8
      ],
      "name": "Adrià Molero-Valenzuela"
    },
    {
      "affs": [
        9
      ],
      "name": "Javier Hernandez-Losa",
      "orcid": "0000-0003-1526-3201"
    },
    {
      "affs": [
        0,
        9
      ],
      "name": "Berta Ferrer"
    },
    {
      "affs": [
        1,
        3,
        10
      ],
      "name": "Holger Heyn",
      "orcid": "0000-0002-3276-1889"
    },
    {
      "affs": [
        11
      ],
      "name": "Eva Muñoz-Couselo",
      "orcid": "0000-0001-7556-7608"
    },
    {
      "affs": [
        0,
        12
      ],
      "name": "Vicenç García-Patos"
    },
    {
      "affs": [
        13
      ],
      "name": "Juan A Recio",
      "orcid": "0000-0002-7320-3832"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8xwndeybs59ps.bib",
  "cited_by": 0,
  "doi": "10.1038/s41467-026-77868-4",
  "fulltext_url": "https://europepmc.org/articles/PMC13686976",
  "id": "8xwndeybs59ps",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://europepmc.org/article/MED/42907443",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2730|Cancer Immunotherapy and Biomarkers"
    ]
  ],
  "openalex": "W7214042224",
  "pdf_url": "https://europepmc.org/articles/PMC13686976?pdf=render",
  "pmcid": "PMC13686976",
  "pmid": "42907443",
  "published": "2026-09-22",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/8xwndeybs59ps.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:57Z",
      "native_id": "MED:42907443",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42907443"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Cancer Immunotherapy and Biomarkers",
      "subfield": "oncology"
    }
  ],
  "title": "p38α orchestrates BRAFV600E-melanoma progression and immunotherapy response via tumor fitness and immune microenvironment modulation.",
  "title_text": "p38α orchestrates BRAFV600E-melanoma progression and immunotherapy response via tumor fitness and immune microenvironment modulation.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:57Z",
  "url": "https://research.draconitic.com/paper/8xwndeybs59ps",
  "venue": "Nature communications",
  "versions": []
}