T Cell Defects and Immunotherapy in Chronic Lymphocytic Leukemia

Abstract

In the past few years, independent studies have highlighted the relevance of the tumor microenvironment (TME) in cancer, revealing a great variety of TME-related predictive markers, as well as identifying novel therapeutic targets in the TME. Cancer immunotherapy targets different components of the immune system and the TME at large in order to reinforce effector mechanisms or relieve inhibitory and suppressive signaling. Currently, it constitutes a clinically validated treatment for many cancers, including chronic lymphocytic leukemia (CLL), an incurable malignancy of mature B lymphocytes with great dependency on microenvironmental signals. Although immunotherapy represents a promising therapeutic option with encouraging results in CLL, the dysfunctional T cell compartment remains a major obstacle in such approaches. In the scope of this review, we outline the current immunotherapeutic treatment options in CLL in the light of recent immunogenetic and functional evidence of T cell impairment. We also highlight possible approaches for overcoming T cell defects and invigorating potent anti-tumor immune responses that would enhance the efficacy of immunotherapy.