Mucosal melanoma is a rare subtype of melanoma originating from mucosal tissues. In its metastatic form it is very aggressive and responds poorly to treatments, including immune checkpoint inhibitors (ICI) such as anti-CTLA4 and anti-PD1 that stimulate anti-tumour immunity. CD8+ T cells constitute the most abundant immune infiltrate in metastatic melanoma, of which the Tissue Resident Memory subset (TRM) is of particular interest. TRM express the highest levels of immune checkpoint molecules, proliferate in response to ICI and correlate with longer disease-free and overall survival.
The immune landscape in mucosal melanoma is still poorly characterized. Therefore, we investigated the CD8+ T and TRM cells infiltrating two subcutaneous metastatic melanoma lesions, resected before and during anti-PD1 treatment at different sites from the same patient. We aimed to understand their capacity to respond to cancer cells and to in vivo and in vitro anti-PD1 treatment.
CD8+ TRM frequency increased with time and anti-PD1 treatment, forming clusters at the tumour margin. Single cell mRNA and paired TCR sequencing revealed similar T cell subsets in both lesions and sharing of clones between TRM, suggesting the presence of common antigens, in agreement with the similar mutational profile of the two metastases. Sorted TRM became more activated upon contact with tumour cells compared to other CD8+ T cells, but neither increased their tumour response in the presence of anti-PD1.
In this patient, TRM are enriched with tumour-specific T cells compared to other CD8+ T cell subsets and ICI treatment increases their presence at the tumour site.