Immune dysfunction in chronic lymphocytic leukemia T cells and lenalidomide as an immunomodulatory drug

Abstract

A new agent that is being used in chronic lymphocytic leukemia (CLL) and is receiving considerable interest is the immunomodulatory drug lenalidomide. The precise anti-CLL mechanism of action of lenalidomide is not yet completely defined. In this perspective article, Drs. Ramsay and Gribben examine the multiple biological effects of lenalidomide on various cell targets that likely contribute to its anti-CLL activity. See related paper on page 1266.

Figure 1.

Lenalidomide repairs chronic lymphocytic leukemia T-cell immune synapse dysfunction. Treatment of both chronic lymphocytic leukemia cells and autologous T cells is required to enhance immunological synapse formation and T-cell functional signaling.

Figure 2.

Lenalidomide restores T-cell actin cytoskeletal signaling (synapse formation and functional activity) and enhances antigen-presenting function of chronic lymphocytic leukemia cells (upregulation of co-stimulatory molecules). NK-mediated ADCC of rituximab-treated chronic lymphocytic leukemia cells is enhanced by pre-incubation of NK cells with lenalidomide before exposure to rituximab-exposed chronic lymphocytic leukemia cells. The immunomodulatory effect of lenalidomide on stromal cells and angiogenic status remains to be fully elucidated.