Sir Peter MacCallum Department of Oncology - Research Publications

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    Accumulation of CD103+ CD8+ T cells in a cutaneous melanoma micrometastasis
    Hochheiser, K ; Aw Yeang, HX ; Wagner, T ; Tutuka, C ; Behren, A ; Waithman, J ; Angel, C ; Neeson, PJ ; Gebhardt, T ; Gyorki, DE (WILEY, 2019)
    OBJECTIVE: The immune system can halt cancer progression by suppressing outgrowth of clinically occult micrometastases in a state of cancer-immune equilibrium. Cutaneous melanoma provides a unique opportunity to study the immune contexture of such lesions, as miniscule skin metastases are accessible to clinical inspection and diagnostic biopsy. METHODS: Here, we analysed by multiplex immunofluorescence microscopy samples from a melanoma patient presenting with an overt and an occult in-transit metastasis (ITM), the latter of which appeared as a small erythematous papule. RESULTS: Microarchitecture and immune composition in the two lesions were vastly different. CD4+ and CD8+ T cells accumulated around the margin of the overt SOX10+ Melan A+ ITM but were largely excluded from the tumor centre. By contrast, the occult micrometastasis contained only few SOX10+ Melan A- melanoma cells which were scattered within a dense infiltrate of T cells, including a prominent population of CD103+ CD8+ T cells resembling tissue-resident memory T (TRM) cells. Notably, almost every single melanoma cell in the micrometastasis was in close proximity to these TRM-like cells. CONCLUSION: Such results support the emerging concept that CD103+ CD8+ TRM cells are key mediators of cancer surveillance and imply an important function of these cells in controlling clinically occult micrometastases in humans.