Key Points
• Source: Journal of Experimental & Clinical Cancer Research (BMC)
• Conclusion/Relevance: “There is still need for more research to understand the effects of each treatment option (monotherapies and combinations) in the tumor environment and current technology can yield insightful data. Thus, it is essential to include broader biomarker analysis in clinical studies, that go beyond analysis of B-cells and include T-cell subpopulations and soluble factors at baseline and different timepoints. Moreover, whatever we learn about immunotherapies in such a paradigmatic immunosuppressed disease as CLL can help improve their efficacy in other tumors where immune function is impaired.”
• In part, the authors of the review examined BTK inhibitors. BTK inhibitors function via transient lymphocytosis secondary to the mobilization of B-cells from lymph nodes, bone marrow, and the spleen to peripheral blood. Furthermore, they elicit changes in the tumor environment secondary to a decrease in the expression of immunosuppressive molecules, including PD-L1, IL-10, CD200 or BTLA in CLL B-cells.
• On a related note, BTK inhibitors also inhibit Tec kinase, ITK, which is a key component of TCR signaling and promotes Th2, T-reg, and Th9 CD4+ cells differentiation and decreases cytotoxic CD8+ and CD4+ Th1 cells differentiation. “This is relevant for tumor control since skewing T-cell differentiation towards a Th2 response would create a pro-tumor environment and cause a decrease of Th1 functions in tumor surveillance. Therefore, the inhibition of ITK also has an impact on the T-cell compartment,” wrote the authors.
• Discussion questions: In which patients would you employ BTK inhibitors? What considerations would you make?