TY - JOUR
T1 - Invariant NKT cells contribute to chronic lymphocytic leukemia surveillance and prognosis
AU - Gorini, Francesca
AU - Azzimonti, Laura
AU - Delfanti, Gloria
AU - Scarfo, Lydia
AU - Scielzo, Cristina
AU - Bertilaccio, Maria Teresa
AU - Ranghetti, Pamela
AU - Gulino, Alessandro
AU - Doglioni, Claudio
AU - Di Napoli, Arianna
AU - Capri, Miriam
AU - Franceschi, Claudio
AU - Caligaris-Cappio, Federico
AU - Ghia, Paolo
AU - Bellone, Matteo
AU - Dellabona, Paolo
AU - Casorati, Giulia
AU - De Lalla, Claudia
N1 - Publisher Copyright:
© 2017 by The American Society of Hematology.
PY - 2017/6/29
Y1 - 2017/6/29
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.
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.
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U2 - 10.1182/blood-2016-11-751065
DO - 10.1182/blood-2016-11-751065
M3 - Article
C2 - 28465341
AN - SCOPUS:85021772525
SN - 0006-4971
VL - 129
SP - 3440
EP - 3451
JO - Blood
JF - Blood
IS - 26
ER -