Title : Immune system exhaustion and immune evasion mechanisms in leukemic cells: A focus on key signaling pathways
Abstract:
The immune system plays a vital role in recognizing and eliminating malignant cells, including those in leukemia. However, leukemic cells develop various mechanisms to evade immune detection and induce immune exhaustion, promoting disease progression. Understanding these mechanisms is critical for developing effective immunotherapies. In leukemia, the tumor microenvironment significantly contributes to Immune exhaustion through the expression of immune checkpoint molecules such as PD-1, CTLA-4, and TIM-3 on T or NK cells, as well as the expression these ligands on leukemic cells including PD-L1, Galectin-9, and PVR. These checkpoints inhibit T cell activation and lead to anergy, rendering T cells less effective in combating tumor. One key mechanism of immune evasion in leukemic cells involves the dysregulation of important signaling pathways. The PI3K/Akt/mTOR pathway is frequently activated in leukemic cells, promoting their survival and proliferation while simultaneously inhibiting T cell activation. Additionally, the aberrant activation of the NF-κB pathway results in the production of immunosuppressive cytokines, such as IL-10 and TGF-β, which further contribute to immune tolerance and exhaustion. Leukemic cells also exploit the JAK/STAT signaling pathway to enhance their interactions with the immune system. For example, activation of STAT3 promotes the expression of genes that facilitate immune evasion and resistance to apoptosis. By secreting factors that engage these pathways, leukemic cells create an immunosuppressive environment that inhibits effective immune responses. These insights into immune exhaustion and evasion highlight the necessity for innovative therapeutic strategies targeting these signaling pathways. Recent advances in immunotherapy, including checkpoint inhibitors and small molecules inhibitors, have demonstrated the potential to restore immune function against leukemic cells. By disrupting the signals that lead to immune exhaustion, these therapies offer new approaches to enhance treatment efficacy. In summary, the mechanisms of immune exhaustion and evasion in leukemic cells are closely linked to critical signaling pathways. Ongoing research in this area is essential for identifying therapeutic targets and developing more effective treatments. Understanding how to reverse immune exhaustion and bolster immune surveillance is key to improving outcomes for patients with leukemia and other hematologic malignancies.
