title: Comparative immune phenotypic analysis of cutaneous Squamous Cell Carcinoma and Intraepidermal Carcinoma in immune-competent individuals: proportional representation of CD8+ T-cells but not FoxP3+ Regulatory T-cells is associated with disease stage.
abstract: Squamous Cell Carcinoma (SCC) is a type of non-melanoma skin cancer prevalent in immune-suppressed transplant recipients and older individuals with a history of chronic sun-exposure. SCC itself is believed to be a late-stage manifestation that can develop from premalignant lesions including Intraepidermal Carcinoma (IEC). Notably, while SCC regression is rare, IEC typically regresses in response to immune modifying topical treatments, however the underlying immunological reasons for these differential responses remain unclear. This study aimed to define whether IEC and SCC are associated with distinct immune profiles. We investigated the immune cell infiltrate of photo-damaged skin, IEC, and SCC tissue using 10-colour flow cytometry following fresh lesion digest. We found that IEC lesions contain higher percentages of CD3+ T-cells than photo-damaged skin, however, the abundance of CD3-CD56+ Natural Killer (NK) cells, CD11c+HLA-DR+ conventional Dendritic Cells (cDC), BDCA-2+HLA-DR+ plasmacytoid DC (pDC), FoxP3+ Regulatory T-cells (T-reg), Vα24+Vβ11+ invariant NKT-cells, and γδ Tcells did not alter with disease stage. Within the total T-cell population, high percentages of CD4+ T-cells were associated with SCC, yet CD8+ T-cells were less abundant in SCC compared with IEC. Our study demonstrates that while IEC lesions contain a higher proportion of T-cells than SCC lesions in general, SCC lesions specifically display a lower abundance of CD8+ T-cells than IEC. We propose that differences in CD8+ T-cell abundance contribute critically to the different capacity of SCC and IEC to regress in response to immune modifying topical treatments. Our study also suggests that a high ratio of CD4+ T-cells to CD8+ T-cells may be a immunological diagnostic indicator of late-stage SCC development in immune-competent patients.
authors.affiliation: The Skin Centre, Pindara Private Hospital, Gold Coast, Australia; Dermatology Research Centre, The University of Queensland, School of Medicine, Translational Research Institute, Brisbane, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Freeman
authors.affiliation: The University of Queensland Diamantina Institute, University of Queensland, Translational Research Institute, Brisbane, Australia.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Bridge
authors.affiliation: The University of Queensland Diamantina Institute, University of Queensland, Translational Research Institute, Brisbane, Australia.
authors.forename: Pirashanthini
authors.initials: P
authors.lastname: Maruthayanar
authors.affiliation: The University of Queensland Diamantina Institute, University of Queensland, Translational Research Institute, Brisbane, Australia.
authors.forename: Nana H
authors.initials: NH
authors.lastname: Overgaard
authors.affiliation: The University of Queensland Diamantina Institute, University of Queensland, Translational Research Institute, Brisbane, Australia.
authors.forename: Ji-Won
authors.initials: JW
authors.lastname: Jung
authors.affiliation: The University of Queensland Diamantina Institute, University of Queensland, Translational Research Institute, Brisbane, Australia.
authors.forename: Fiona
authors.initials: F
authors.lastname: Simpson
authors.affiliation: Dermatology Research Centre, The University of Queensland, School of Medicine, Translational Research Institute, Brisbane, Australia.
authors.forename: Tarl W
authors.initials: TW
authors.lastname: Prow
authors.affiliation: Dermatology Research Centre, The University of Queensland, School of Medicine, Translational Research Institute, Brisbane, Australia.
authors.forename: H Peter
authors.initials: HP
authors.lastname: Soyer
authors.affiliation: The University of Queensland Diamantina Institute, University of Queensland, Translational Research Institute, Brisbane, Australia.
authors.forename: Ian H
authors.initials: IH
authors.lastname: Frazer
authors.affiliation: The Skin Centre, Pindara Private Hospital, Gold Coast, Australia; Dermatology Research Centre, The University of Queensland, School of Medicine, Translational Research Institute, Brisbane, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Freeman
authors.affiliation: The University of Queensland Diamantina Institute, University of Queensland, Translational Research Institute, Brisbane, Australia.
authors.forename: James W
authors.initials: JW
authors.lastname: Wells
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D039521:CD11c Antigen / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D019002:CD56 Antigen / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology*; D002294:Carcinoma, Squamous Cell / Q000276:immunology*; D002465:Cell Movement; D018450:Disease Progression; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000166:cytology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012867:Skin / Q000528:radiation effects; D012878:Skin Neoplasms / Q000276:immunology*; D013472:Sunlight / Q000009:adverse effects; D050378:T-Lymphocytes, Regulatory / Q000166:cytology*
chemical_list: D039521:CD11c Antigen; D017252:CD3 Complex; D019002:CD56 Antigen; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D006684:HLA-DR Antigens; C522918:NCAM1 protein, human