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, 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, Emanuela Marcenaro, Paolo A. Ascierto, Valter AgostiElio Gulletta, Ennio Carbone, Alessandro Moretta

Risultato della ricerca: Article

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
RivistaDefault journal
Volume7
Stato di pubblicazionePublished - 2019

All Science Journal Classification (ASJC) codes

  • Immunology
  • Cancer Research

Cita questo

Accumulation of Circulating CCR7+ Natural Killer Cells Marks Melanoma Evolution and Reveals a CCL19-Dependent Metastatic Pathway. / Turdo, Alice; Todaro, Matilde; Apuzzo, Tiziana; Capone, Mariaelena; Tallerico, Rossana; Pesce, Silvia; Ventura, Valeria; Garofalo, Cinzia; Madonna, Gabriele; Grimaldi, Antonio M.; Costanzo, Francesco Saverio; Giovannone, Emilia Dora; Cristiani, Costanza Maria; Mallardo, Domenico; Karre, Klas; Zotto, Genny Del; Rizzo, Aroldo; Marcenaro, Emanuela; Ascierto, Paolo A.; Agosti, Valter; Gulletta, Elio; Carbone, Ennio; Moretta, Alessandro.

In: Default journal, Vol. 7, 2019, pag. 841-852.

Risultato della ricerca: Article

Turdo, A, Todaro, M, Apuzzo, T, Capone, M, Tallerico, R, Pesce, S, Ventura, V, Garofalo, C, Madonna, G, Grimaldi, AM, Costanzo, FS, Giovannone, ED, Cristiani, CM, Mallardo, D, Karre, K, Zotto, GD, Rizzo, A, Marcenaro, E, Ascierto, PA, Agosti, V, Gulletta, E, Carbone, E & Moretta, A 2019, 'Accumulation of Circulating CCR7+ Natural Killer Cells Marks Melanoma Evolution and Reveals a CCL19-Dependent Metastatic Pathway', Default journal, vol. 7, pagg. 841-852.
Turdo, Alice ; Todaro, Matilde ; Apuzzo, Tiziana ; Capone, Mariaelena ; Tallerico, Rossana ; Pesce, Silvia ; Ventura, Valeria ; Garofalo, Cinzia ; Madonna, Gabriele ; Grimaldi, Antonio M. ; Costanzo, Francesco Saverio ; Giovannone, Emilia Dora ; Cristiani, Costanza Maria ; Mallardo, Domenico ; Karre, Klas ; Zotto, Genny Del ; Rizzo, Aroldo ; Marcenaro, Emanuela ; Ascierto, Paolo A. ; Agosti, Valter ; Gulletta, Elio ; Carbone, Ennio ; Moretta, Alessandro. / Accumulation of Circulating CCR7+ Natural Killer Cells Marks Melanoma Evolution and Reveals a CCL19-Dependent Metastatic Pathway. In: Default journal. 2019 ; Vol. 7. pagg. 841-852.
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title = "Accumulation of Circulating CCR7+ Natural Killer Cells Marks Melanoma Evolution and Reveals a CCL19-Dependent Metastatic Pathway",
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.",
keywords = "Melanoma, NK cells, cancer stem cells, immune surveillance, metastasis",
author = "Alice Turdo and Matilde Todaro and Tiziana Apuzzo and Mariaelena Capone and Rossana Tallerico and Silvia Pesce and Valeria Ventura and Cinzia Garofalo and Gabriele Madonna and Grimaldi, {Antonio M.} and Costanzo, {Francesco Saverio} and Giovannone, {Emilia Dora} and Cristiani, {Costanza Maria} and Domenico Mallardo and Klas Karre and Zotto, {Genny Del} and Aroldo Rizzo and Emanuela Marcenaro and Ascierto, {Paolo A.} and Valter Agosti and Elio Gulletta and Ennio Carbone and Alessandro Moretta",
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T1 - Accumulation of Circulating CCR7+ Natural Killer Cells Marks Melanoma Evolution and Reveals a CCL19-Dependent Metastatic Pathway

AU - Turdo, Alice

AU - Todaro, Matilde

AU - Apuzzo, Tiziana

AU - Capone, Mariaelena

AU - Tallerico, Rossana

AU - Pesce, Silvia

AU - Ventura, Valeria

AU - Garofalo, Cinzia

AU - Madonna, Gabriele

AU - Grimaldi, Antonio M.

AU - Costanzo, Francesco Saverio

AU - Giovannone, Emilia Dora

AU - Cristiani, Costanza Maria

AU - Mallardo, Domenico

AU - Karre, Klas

AU - Zotto, Genny Del

AU - Rizzo, Aroldo

AU - Marcenaro, Emanuela

AU - Ascierto, Paolo A.

AU - Agosti, Valter

AU - Gulletta, Elio

AU - Carbone, Ennio

AU - Moretta, Alessandro

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

KW - Melanoma

KW - NK cells

KW - cancer stem cells

KW - immune surveillance

KW - metastasis

UR - http://hdl.handle.net/10447/356373

M3 - Article

VL - 7

SP - 841

EP - 852

JO - Default journal

JF - Default journal

ER -