Accumulation of Circulating CCR7+ Natural Killer Cells Marks Melanoma Evolution and Reveals a CCL19-Dependent Metastatic Pathway

Alice Turdo, Matilde Todaro, Tiziana Apuzzo, Mariaelena Capone, Rossana Tallerico, Aroldo Rizzo, Silvia Pesce, Valeria Ventura, Cinzia Garofalo, Gabriele Madonna, Antonio M. Grimaldi, Francesco Saverio Costanzo, Emilia Dora Giovannone, Costanza Maria Cristiani, Domenico Mallardo, Klas Karre, Genny Del Zotto, Aroldo Rizzo, Genny Del Zotto, Emanuela MarcenaroPaolo A. Ascierto, Valter Agosti, Elio Gulletta, Ennio Carbone, Alessandro Moretta

Risultato della ricerca: Article

3 Citazioni (Scopus)

Abstract

Immune checkpoint blockade therapy has changed prognoses for many melanoma patients. However, immune responses that correlate with clinical progression of the disease are still poorly understood. To identify immune responses correlating with melanoma clinical evolution, we analyzed serum cytokines as well as circulating NK and T-cell subpopulations from melanoma patients. The patients' immune profiles suggested that melanoma progression leads to changes in peripheral blood NK and T-cell subsets. Stage IV melanoma was characterized by an increased frequency of CCR7+CD56bright NK cells as well as high serum concentrations of the CCR7 ligand CCL19. CCR7 expression and CCL19 secretion were also observed in melanoma cell lines. The CCR7+ melanoma cell subpopulation coexpressed PD-L1 and Galectin-9 and had stemness properties. Analysis of melanoma-derived cancer stem cells (CSC) showed high CCR7 expression; these CSCs were efficiently recognized and killed by NK cells. An accumulation of CCR7+, PD-L1+, and Galectin-9+ melanoma cells in melanoma metastases was demonstrated ex vivo Altogether, our data identify biomarkers that may mark a CCR7-driven metastatic melanoma pathway.
Lingua originaleEnglish
pagine (da-a)841-852
Numero di pagine12
RivistaCancer immunology research
Volume7
Stato di pubblicazionePublished - 2019

All Science Journal Classification (ASJC) codes

  • Immunology
  • Cancer Research

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    Turdo, A., Todaro, M., Apuzzo, T., Capone, M., Tallerico, R., Rizzo, A., Pesce, S., Ventura, V., Garofalo, C., Madonna, G., Grimaldi, A. M., Costanzo, F. S., Giovannone, E. D., Cristiani, C. M., Mallardo, D., Karre, K., Zotto, G. D., Rizzo, A., Zotto, G. D., ... Moretta, A. (2019). Accumulation of Circulating CCR7+ Natural Killer Cells Marks Melanoma Evolution and Reveals a CCL19-Dependent Metastatic Pathway. Cancer immunology research, 7, 841-852.