Fig. 6

Therapeutic strategies targeting CD4⁺ CTLs. Therapeutic strategies targeting CD4⁺ CTLs can be divided into three categories: selective inhibitors (a), adoptive cell therapy (b), and virus-induced CD4⁺ CTLs (c). Selective inhibitors modulate the activation, proliferation, and function of CD4⁺ CTLs by targeting costimulatory molecules, cytokines, and regulatory factors associated with these cells, thereby influencing the immune balance of the body. Adoptive cell therapy, particularly CAR-T-cell therapy, involves isolating CD4⁺ CTLs from patients, editing these cells ex vivo to acquire chimeric receptors, and then reintroducing them to increase their specificity and cytotoxicity against specific antigens. Virus-induced CD4⁺ CTLs leverage the endogenous and exogenous loading of viral antigen peptides onto tumor MHC II molecules, mimicking local reinfection with a previously encountered pathogen, which triggers the reactivation of virus-specific CD4⁺ CTLs to target and eliminate tumor cells. TNFR tumor necrosis factor receptor. Created at https://BioRender.com