PI3K Isoforms in CD8⁺ T Cell Development and Function

CD8⁺ T cells are an essential part of the immune system and play a vital role in defending against tumors and infections. The phosphoinositide-3-kinase (PI3K), especially class I, is involved in numerous interrelated signaling pathways which control CD8⁺ T cell development, maturation, migration, activation, and differentiation. While CD8⁺ T lymphocytes express all class I PI3K isoforms (PI3Kα, PI3Kβ, PI3Kδ, and PI3Kγ), isoform-specific functions, especially for PI3Kα and PI3Kβ have not been fully elucidated. A few studies suggest the important role of p110δ and p110γ in CD8⁺ T cell activation, signaling, chemotaxis and function and several clinical trials are currently testing the effect of isoform-specific inhibitors in various types of cancers, including Indolent Non-Hodgkin Lymphoma, Peripheral T cell Lymphoma, Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, non-small cell lung carcinoma (NSCLC), head & neck cancer, and breast cancer. This chapter summarizes current knowledge of the roles of various PI3K isoforms and downstream signaling pathways in regulating CD8⁺ T cell fate, including cell proliferation, migration, and memory generation. We also discuss certain clinical trials employing PI3K inhibitors for cancer therapy, their limitations, and future perspectives.