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

Abstract

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.

Ptpn2 and KLRG1 regulate the generation and function of tissue-resident memory CD8+ T cells in skin

“…In line with this, we and others have recently shown that genetic deletion of Ptpn2 in total T cells, CD8 + T cells or chimeric antigen receptor T cells augments cancer immunity ( LaFleur et al, 2019 ; Wiede et al, 2020 ). In case of cutaneous melanoma, Ptpn2 deficiency indeed results in enhanced generation of tumor-specific CD69 + CD103 + T RM cells ( Wiede et al, 2020 ), and we have previously shown that these cells can drive long-term melanoma control ( Edwards et al, 2018 ; Hochheiser et al, 2019 ; Park et al, 2019a ). Thus, while Ptpn2 modulates the generation of memory precursor cells in a context-dependent manner, it does not appear to influence the process of T RM cell differentiation in peripheral tissues per se.…”

Tissue-Resident Memory T Cells in Skin Diseases: A Systematic Review

“…The expansion of tumor-resident CD8 + , CD103 + T cells have been shown to predict treatment response in patients treated with immune checkpoint inhibitors [119]. Furthermore, a case report corroborated that TRMs were involved in melanoma cancer-immune surveillance and cancer-immune equilibrium [31]. CD8 + CD103 + TRM cells bearing the marker CD39, which is involved in immunosuppression, have been found in increased numbers in melanomas compared with a variety of other tumor types [32].…”

Dormancy of cutaneous melanoma

“…NK cells and tissue-resident CD8 + T cells prevent outgrowth of metastases in murine and human melanoma models (Fig. 2B) [129][130][131]. The effect is postulated to be rather cytostatic than cytotoxic [61].…”