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Dual PD1/LAG3 immune checkpoint blockade limits tumor development in a murine model of chronic lymphocytic leukemia

Wierz, M., Pierson, S., Guyonnet, L. et al.

Tissue-infiltrating chronic lymphocytic leukemia (CLL) cells come in direct contact with both accessory stromal and immune cells that compose the tumor microenvironment (TME). The proliferation and survival of CLL cells is highly dependent on complex interactions with nonmalignant cells of the TME. Malignant cells are capable of suppressing antitumor immune responses by several mechanisms to escape immune surveillance, including the dysregulation of immune checkpoints, which are surface proteins that regulate immune cell activation. It has been demonstrated that CLL cells overexpress programmed cell death ligand 1 (PD-L1), resulting in increased PD-L1/PD1 signaling and, consequently, CD8+ T-cell functional silencing. Immunotherapy aims to stimulate antitumor activity by reactivating the immune system and showed encouraging results in preclinical CLL studies. Here, we established an extensive cartography of immune cell subsets populating the leukemic microenvironment in a murine model of CLL, as well as their immune checkpoint profile, and evaluated the efficacy of a relevant dual immunotherapy in a preclinical study.

Citation

Wierz, M., Pierson, S., Guyonnet, L. et al. "Dual PD1/LAG3 immune checkpoint blockade limits tumor development in a murine model of chronic lymphocytic leukemia" Blood (2018): 1,617–21