biostudies-literatureUnknownPrakrithi PCutaneous squamous cell carcinoma (cSCC), basal cell carcinoma (BCC), and melanoma, the three major types of skin cancer, account for over 70% of all cancer cases. Despite their prevalence, the skin cancer microenvironment remains poorly characterized, both in the outer skin layer where the cancer originates and at the deeper junctional and dermal layers into which it progresses. To address this, we integrated 12 complementary spatial single-cell technologies to construct orthogonally-validated cell signatures, spatial maps, and interactomes for cSCC, BCC, and melanoma. We comprehensively compared and integrated these spatial methods and provided practical guidelines on experimental design. Integrating four spatial transcriptomics platforms, we found keratinocyte cancer signatures, includibioRxiv : the preprint server for biology2025.07.25.666708https://www.ebi.ac.uk/biostudies/studies/S-EPMC12324176biostudies-literatureIntegrating 12 Spatial and Single Cell Technologies to Characterise Tumour Neighbourhoods and Cellular Interactions in three Skin Cancer Types.PMC12324176Zhang FPham DHockey LTan SXGregory MTZhang MO'Brien BMulay OTuong KXiong ZBrown KMLeon MCruz JGMurphy SRTeoh SMReitz ZJin XMcMillan CGrice LFTan XKillingbeck EELandi MTMuller DPrakrithi PFrazer IStark MSDevitt KHenricson JLaw MHKim ESeviiri MKulasinghe ANewman AKao YCIles MMWarren SEMuller NMVo TNi GNguyen QEverest-Dass ALuu HNKhosrotehrani KSoyer HPVu HTran MKumari SAnderson CKim YCauser APan LSato HfalseIntegrating 12 Spatial and Single Cell Technologies to Characterise Tumour Neighbourhoods and Cellular Interactions in three Skin Cancer Types.Cutaneous squamous cell carcinoma (cSCC), basal cell carcinoma (BCC), and melanoma, the three major types of skin cancer, account for over 70% of all cancer cases. Despite their prevalence, the skin cancer microenvironment remains poorly characterized, both in the outer skin layer where the cancer originates and at the deeper junctional and dermal layers into which it progresses. To address this, we integrated 12 complementary spatial single-cell technologies to construct orthogonally-validated cell signatures, spatial maps, and interactomes for cSCC, BCC, and melanoma. We comprehensively compared and integrated these spatial methods and provided practical guidelines on experimental design. Integrating four spatial transcriptomics platforms, we found keratinocyte cancer signatures, includi2025-01-01T00:00:00Z2025 Jul2026-04-07T18:44:16.228Z2026-04-07T16:46:48.364ZS-EPMC123241764076655510.1101/2025.07.25.666708