{
  "abstract": "Background Ultraviolet radiation (UVR) affects local cutaneous and systemic immunity acutely. The wavelength, pattern and intensity of UVR exposure, individual skin phototype and immune state of individuals modulate the impact of UVR systemically. Local cutaneous immunity after UVR leads to immunosuppression that impacts melanoma. However, the effects of systemic UVR-induced changes on solid cancer therapy are not known.Methods We investigated the impact of repeated UVR exposure on systemic immunity and immune checkpoint blockade (ICB) tumor responses in colorectal cancer and melanoma mouse models.Results Animals exposed to chronic UVR exhibit decreased ICB response, which is mediated by systemic factors. Repeated UVR exposure expanded systemic lymphocyte populations and contracted total systemic myeloid cells. Specifically, UVR expanded peripheral blood CD4 + regulatory T cells (Tregs), which in turn led to greater Treg infiltration and immunosuppression in colorectal and skin cancer, and colorectal ICB-resistant tumors expressed unique pathways of ICB resistance due to systemic UVR. The response to ICB was restored with systemic pharmacological depletion of Tregs. In preliminary human data, there is an association between the molecular evidence of repeated UVR exposure in dermal fibroblasts and higher systemic Tregs.Discussion Our data indicate that patients with melanoma and other cancers on immunotherapy should avoid repeated sun exposure.",
  "authors": [
    {
      "affiliations": [
        "Skin Cancer and Ageing Lab, Cancer Research UK Manchester Institute",
        "The Oglesby Cancer Research Building, The University of Manchester, Manchester, UK"
      ],
      "name": "Pedro Durao"
    },
    {
      "affiliations": [
        "Skin Cancer and Ageing Lab, Cancer Research UK Manchester Institute",
        "The Oglesby Cancer Research Building, The University of Manchester, Manchester, UK"
      ],
      "name": "Timothy Budden"
    },
    {
      "affiliations": [
        "Skin Cancer and Ageing Lab, Cancer Research UK Manchester Institute",
        "The Oglesby Cancer Research Building, The University of Manchester, Manchester, UK"
      ],
      "name": "Karthik Mallela"
    },
    {
      "affiliations": [
        "Skin Cancer and Ageing Lab, Cancer Research UK Manchester Institute",
        "The Oglesby Cancer Research Building, The University of Manchester, Manchester, UK"
      ],
      "name": "Martha Gutteridge"
    },
    {
      "affiliations": [
        "Skin Cancer and Ageing Lab, Cancer Research UK Manchester Institute",
        "The Oglesby Cancer Research Building, The University of Manchester, Manchester, UK"
      ],
      "name": "Isabella Mataloni"
    },
    {
      "affiliations": [
        "Skin Cancer and Ageing Lab, Cancer Research UK Manchester Institute",
        "The Oglesby Cancer Research Building, The University of Manchester, Manchester, UK"
      ],
      "name": "Shilpa Gurung"
    },
    {
      "affiliations": [
        "Skin Cancer and Ageing Lab, Cancer Research UK Manchester Institute",
        "The Oglesby Cancer Research Building, The University of Manchester, Manchester, UK"
      ],
      "name": "Mirco Mastrangelo"
    },
    {
      "affiliations": [
        "Division of Immunology, Immunity to Infection and Respiratory Medicine, The University of Manchester, Manchester, UK"
      ],
      "name": "Luke Roberts"
    },
    {
      "affiliations": [
        "Cancer Research UK Flow Cytometry Facility, Cancer Research UK Manchester Institute",
        "The Oglesby Cancer Research Building, The University of Manchester, Manchester, UK"
      ],
      "name": "Antonia Banyard"
    },
    {
      "affiliations": [
        "Cancer Research UK Histology Facility, Cancer Research UK Manchester Institute",
        "The University of Manchester, Manchester, UK"
      ],
      "name": "Garry Ashton"
    },
    {
      "affiliations": [
        "Centre for Gene Therapy and Regenerative Medicine, School of Basic and Medical Biosciences",
        "Faculty of Life Sciences and Medicine, King’s College London, London, UK",
        "Division of Infection Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK"
      ],
      "name": "Graham M Lord"
    },
    {
      "affiliations": [
        "Division of Infection Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK"
      ],
      "name": "Adam Hurlstone"
    },
    {
      "affiliations": [
        "The Christie NHS Foundation Trust, Manchester, UK",
        "Division of Cancer Sciences, University of Manchester, Manchester, UK",
        "National Biomarker Center, Cancer Research UK, Manchester, UK"
      ],
      "name": "Sara Valpione"
    },
    {
      "affiliations": [
        "Skin Cancer and Ageing Lab, Cancer Research UK Manchester Institute",
        "The Oglesby Cancer Research Building, The University of Manchester, Manchester, UK",
        "NIHR Manchester Biomedical Research Centre, Manchester, UK",
        "Department of Dermatology, Salford Royal NHS Foundation Trust, The University of Manchester, Manchester, UK"
      ],
      "name": "Amaya Viros"
    }
  ],
  "title": "Systemic immunosuppression from ultraviolet radiation exposure inhibits cancer immunotherapy",
  "uid": "e16b2d1e-c77e-540a-8f7c-b69ca47990c0"
}