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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 The authors investigated the impact of repeated UVR exposure on systemic immunity and immune checkpoint blockade (ICB) tumour 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 tumours 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.
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 The authors investigated the impact of repeated UVR exposure on systemic immunity and immune checkpoint blockade (ICB) tumour 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 tumours 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.
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“We are so pleased to have received the funding to enable us to test our hypothesis in the lab. If we can create a new medicine that can precisely target a specific type of cell within the tumour, and restore anti-cancer immune responses, this will be a game-changer for oesophageal cancer patients “
Sara Valpione
Former Institute Clinical Fellow and now Clinician in Residence within the CRUK National Biomarker Centre
“My charity bake sales – known as “David’s Great British Bake Off” – are always a hit, home baked products taste so much better than shop bought and are greatly appreciated by staff!”
David Jenkins
Purchasing Officer
“We’ve seen some remarkable responses, with an improvement for some patients within days. This is an early phase trial so there’s a lot more work to do. But the data we have so far is very encouraging and could help many thousands of people in the future”
Tim Somervaille
Senior Group Leader
“It is a pleasure to introduce my team who work to deliver our research goals. We work in a friendly and collaborative environment, supporting each other’s projects. “
Amaya Virós
CRUK Advanced Clinician Scientist Fellow
“We are so pleased to have received the funding to enable us to test our hypothesis in the lab. If we can create a new medicine that can precisely target a specific type of cell within the tumour, and restore anti-cancer immune responses, this will be a game-changer for oesophageal cancer patients “
Sara Valpione
Former Institute Clinical Fellow and now Clinician in Residence within the CRUK National Biomarker Centre
“My charity bake sales – known as “David’s Great British Bake Off” – are always a hit, home baked products taste so much better than shop bought and are greatly appreciated by staff!”
David Jenkins
Purchasing Officer
“We’ve seen some remarkable responses, with an improvement for some patients within days. This is an early phase trial so there’s a lot more work to do. But the data we have so far is very encouraging and could help many thousands of people in the future”
Tim Somervaille
Senior Group Leader
“It is a pleasure to introduce my team who work to deliver our research goals. We work in a friendly and collaborative environment, supporting each other’s projects. “
Amaya Virós
CRUK Advanced Clinician Scientist Fellow