DNA Damage Activates Cgas-Sting Pathway Facilitating NK Cell Recognition and Clearance of T-Cell Acute Lymphoblastic Leukemia

T-cell acute lymphoblastic leukemia (T-ALL) are tumors characterized by abnormal clones of T lymphocytes. Traditional chemotherapy and transplantation approaches continue to face risks of treatment failure and patient mortality. While immunotherapy has shown remarkable efficacy in solid tumors and B cell malignancies, T-ALL's lack of unique antigen targets and shared antigens with normal T cells present significant challenges for its immunotherapy. Inducing DNA damage to prompt T-ALL cells to active cGAS-STING pathway can enhance NK cell recognition of target cells, offering a novel adjunctive treatment method. Experimental results indicate that DNA damage-mediated activation of the cGAS-STING signaling pathway, and even promotes the expression of NK cell-stimulatory antigens in tumor cells, facilitating the clearance of T-ALL by NK cells. DNA damage therapy is ineffective in NOD/SCID mouse models of T-ALL, but DNA damage repair inhibitors can enhance the in vivo clearance of T-ALL in immunocompetent mice. Therefore, identifying methods to increase the immunogenicity of T-ALL, thus promoting their recognition and recruitment by the immune system, represents a new therapeutic strategy.

No relevant conflicts of interest to declare.