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

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.

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.

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.

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.