Invariant NKT cells contribute to chronic lymphocytic leukemia surveillance and prognosis

F Gorini, L Azzimonti, G Delfanti, L Scarfò, C Scielzo, MT Bertilaccio, P Ranghetti, A Gulino, C Doglioni, Arianna Di Napoli, M Capri, C Franceschi, F Caligaris-Cappio, P Ghia, M Bellone, P Dellabona, G Casorati, C De Lalla

Research output: Contribution to journalArticle

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Abstract

Chronic lymphocytic leukemia (CLL) is characterized by the expansion of malignantCD51 B lymphocytes in blood, bone marrow, and lymphoid organs. CD1d-restricted invariant natural killer T (iNKT) cells are innate-like T lymphocytes strongly implicated in tumor surveillance.Weinvestigated the impact of iNKT cells in the natural history of the disease in the Em-Tcl1 (Tcl1) CLL mouse model and 68 CLL patients.Wefound that Tcl1-CLL cells express CD1d and that iNKT cells critically delay disease onset but become functionally impaired upon disease progression. In patients, disease progression correlates with high CD1d expression on CLL cells and impaired iNKT cells. Conversely, disease stability correlates with negative or low CD1d expression on CLL cells and normal iNKT cells, suggesting indirect leukemia control. iNKT cells indeed hinder CLL survival in vitro by restraining CD1d-expressing nurse-like cells, a relevant proleukemia macrophage population. Multivariable analysis identified iNKT cell frequency as an independent predictor of disease progression. Together, these results support the contribution of iNKT cells to CLL immune surveillance and highlight iNKT cell frequency as a prognostic marker for disease progression. © 2017 by The American Society of Hematology.
Original languageEnglish
Pages (from-to)3440-3451
Number of pages12
JournalBlood
Volume129
Issue number26
DOIs
Publication statusPublished - 2017

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Natural Killer T-Cells
T-cells
B-Cell Chronic Lymphocytic Leukemia
Disease Progression
Lymphocytes
Macrophages
Leukemia
B-Lymphocytes
Tumors
Bone Marrow
Nurses
Bone
Blood
T-Lymphocytes
Survival

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Invariant NKT cells contribute to chronic lymphocytic leukemia surveillance and prognosis. / Gorini, F; Azzimonti, L; Delfanti, G; Scarfò, L; Scielzo, C; Bertilaccio, MT; Ranghetti, P; Gulino, A; Doglioni, C; Di Napoli, Arianna; Capri, M; Franceschi, C; Caligaris-Cappio, F; Ghia, P; Bellone, M; Dellabona, P; Casorati, G; De Lalla, C.

In: Blood, Vol. 129, No. 26, 2017, p. 3440-3451.

Research output: Contribution to journalArticle

Gorini, F, Azzimonti, L, Delfanti, G, Scarfò, L, Scielzo, C, Bertilaccio, MT, Ranghetti, P, Gulino, A, Doglioni, C, Di Napoli, A, Capri, M, Franceschi, C, Caligaris-Cappio, F, Ghia, P, Bellone, M, Dellabona, P, Casorati, G & De Lalla, C 2017, 'Invariant NKT cells contribute to chronic lymphocytic leukemia surveillance and prognosis', Blood, vol. 129, no. 26, pp. 3440-3451. https://doi.org/10.1182/blood-2016-11-751065
Gorini, F ; Azzimonti, L ; Delfanti, G ; Scarfò, L ; Scielzo, C ; Bertilaccio, MT ; Ranghetti, P ; Gulino, A ; Doglioni, C ; Di Napoli, Arianna ; Capri, M ; Franceschi, C ; Caligaris-Cappio, F ; Ghia, P ; Bellone, M ; Dellabona, P ; Casorati, G ; De Lalla, C. / Invariant NKT cells contribute to chronic lymphocytic leukemia surveillance and prognosis. In: Blood. 2017 ; Vol. 129, No. 26. pp. 3440-3451.
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AU - Azzimonti, L

AU - Delfanti, G

AU - Scarfò, L

AU - Scielzo, C

AU - Bertilaccio, MT

AU - Ranghetti, P

AU - Gulino, A

AU - Doglioni, C

AU - Di Napoli, Arianna

AU - Capri, M

AU - Franceschi, C

AU - Caligaris-Cappio, F

AU - Ghia, P

AU - Bellone, M

AU - Dellabona, P

AU - Casorati, G

AU - De Lalla, C

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N2 - Chronic lymphocytic leukemia (CLL) is characterized by the expansion of malignantCD51 B lymphocytes in blood, bone marrow, and lymphoid organs. CD1d-restricted invariant natural killer T (iNKT) cells are innate-like T lymphocytes strongly implicated in tumor surveillance.Weinvestigated the impact of iNKT cells in the natural history of the disease in the Em-Tcl1 (Tcl1) CLL mouse model and 68 CLL patients.Wefound that Tcl1-CLL cells express CD1d and that iNKT cells critically delay disease onset but become functionally impaired upon disease progression. In patients, disease progression correlates with high CD1d expression on CLL cells and impaired iNKT cells. Conversely, disease stability correlates with negative or low CD1d expression on CLL cells and normal iNKT cells, suggesting indirect leukemia control. iNKT cells indeed hinder CLL survival in vitro by restraining CD1d-expressing nurse-like cells, a relevant proleukemia macrophage population. Multivariable analysis identified iNKT cell frequency as an independent predictor of disease progression. Together, these results support the contribution of iNKT cells to CLL immune surveillance and highlight iNKT cell frequency as a prognostic marker for disease progression. © 2017 by The American Society of Hematology.

AB - Chronic lymphocytic leukemia (CLL) is characterized by the expansion of malignantCD51 B lymphocytes in blood, bone marrow, and lymphoid organs. CD1d-restricted invariant natural killer T (iNKT) cells are innate-like T lymphocytes strongly implicated in tumor surveillance.Weinvestigated the impact of iNKT cells in the natural history of the disease in the Em-Tcl1 (Tcl1) CLL mouse model and 68 CLL patients.Wefound that Tcl1-CLL cells express CD1d and that iNKT cells critically delay disease onset but become functionally impaired upon disease progression. In patients, disease progression correlates with high CD1d expression on CLL cells and impaired iNKT cells. Conversely, disease stability correlates with negative or low CD1d expression on CLL cells and normal iNKT cells, suggesting indirect leukemia control. iNKT cells indeed hinder CLL survival in vitro by restraining CD1d-expressing nurse-like cells, a relevant proleukemia macrophage population. Multivariable analysis identified iNKT cell frequency as an independent predictor of disease progression. Together, these results support the contribution of iNKT cells to CLL immune surveillance and highlight iNKT cell frequency as a prognostic marker for disease progression. © 2017 by The American Society of Hematology.

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