Accumulation of CD103⁺ CD8⁺ T cells in a cutaneous melanoma micrometastasis

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 (T_RM) cells. Notably, almost every single melanoma cell in the micrometastasis was in close proximity to these T_RM-like cells. Conclusion: Such results support the emerging concept that CD103⁺ CD8⁺ T_RM cells are key mediators of cancer surveillance and imply an important function of these cells in controlling clinically occult micrometastases in humans.