Invariant NKT cells contribute to chronic lymphocytic leukemia surveillance and prognosis

Francesca Gorini, Laura Azzimonti, Gloria Delfanti, Lydia Scarfò, Cristina Scielzo, Maria Teresa Bertilaccio, Pamela Ranghetti, Alessandro Gulino, Claudio Doglioni, Arianna Di Napoli, Miriam Capri, Claudio Franceschi, Federico Caligaris-Cappio, Paolo Ghia, Matteo Bellone, Paolo Dellabona, Giulia Casorati and Claudia de Lalla

Key Points

  • iNKT cells control CLL progression in both mice and patients and this inversely correlates with CD1d expression by leukemia cells.

  • Human iNKT cells indirectly hinder CLL survival by restraining proleukemia monocyte-derived nurse-like cells.

Publisher's Note: There is an Inside Blood Commentary on this article in this issue.


Chronic lymphocytic leukemia (CLL) is characterized by the expansion of malignant CD5+ 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. We investigated the impact of iNKT cells in the natural history of the disease in the Eμ-Tcl1 (Tcl1) CLL mouse model and 68 CLL patients. We found 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.

  • Submitted November 15, 2016.
  • Accepted April 12, 2017.
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