Dendritic cells recruitment in melanoma metastasis treated by electrochemotherapy.
Electrochemotherapy (ECT) is a novel treatment for recurrent or in-transit unresectable melanoma metastases based on the administration of anti-neoplastic drugs followed by cancer cell electroporation. Whether ECT can also induce anti-tumour immunity is unclear. We addressed this issue investigating the presence of dendritic cells (DCs) in the inflammatory infiltrate of ECT-treated lesions. Biopsies from melanoma patients (n = 9) were taken before ECT (T0), at d7 and d14 after treatment and studied by immunofluorescence with DCs-related antibodies. Epidermal Langerin(+) Langerhans cells (LCs) were the most represented subset before treatment. ECT induced a significant reduction in epidermal LCs number at d7 (p < 0.001), while they were completely replaced at d14. Similarly, the few LCs observed intermingled with metastatic melanoma cells at T0 decreased after treatment (p < 0.001), suggesting an ECT-induced activation of LCs. Consistently, at d1 after ECT (n = 3 patients), LCs were found to express CCR7, which mediates LCs migration to regional lymph nodes, and CD83, the typical DCs maturation marker. In contrast, plasmacytoid DCs (pDCs) were not present at T0, but significantly increased after ECT both in melanoma metastasis (p < 0.001) and perilesionally (p < 0.05). Similarly, CD1c(+) dermal DCs (dDCs), observed in low number before ECT, strongly increased at d7 and even more at d14 (p < 0.05 and p < 0.001, respectively). Notably, some dDCs expressed CD83. These data suggest that ECT promotes LCs migration from the tumour to draining lymph nodes and pDCs and dDCs recruitment at the site of the lesion. These findings may help to design new strategies of in situ DCs vaccination in cancer patients.
Plastic Surgery Unit, Regional Melanoma Referral Center, Tuscan Tumour Institute, Santa Maria Annunziata Hospital, Via Antella 58, 50012 Bagno a Ripoli, Florence, Italy. gianni.gerlini@asf.toscana.it
Gianni
G
Gerlini
Serena
S
Sestini
Paola
P
Di Gennaro
Carmelo
C
Urso
Nicola
N
Pimpinelli
Lorenzo
L
Borgognoni
D002465:Cell Movement / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D053672:Electrochemotherapy; D000078404:Epidermal Cells; D004817:Epidermis / Q000276:immunology; D005455:Fluorescent Antibody Technique; D006801:Humans; D007801:Langerhans Cells / Q000166:cytology / Q000276:immunology*; D008545:Melanoma / Q000276:immunology* / Q000556:secondary / Q000628:therapy; D012878:Skin Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D014407:Tumor Cells, Cultured