Fig. 3

Novel immunotherapy approaches in MDS. A Genetically modified tumor cells are used in GVAX vaccine to release GM-CSF, which enhances the immune response against tumor cells. GVAX promotes DC recruitment and activation to increase the ability of the immune system to recognize and destroy tumor cells. Apoptotic bodies produced by irradiated tumor cells are taken up by DCs, contributing to DC maturation. B Dendritic cell vaccines are generated by loading patient-derived DCs with TAA/LAA to trigger a targeted immune response against tumor cells. These vaccines can be prepared by expressing TAA/LAA on MHC-I/II in DCs loaded with peptides, nucleic acids, viral vectors, or apoptotic tumor bodies. C Peptide vaccines are based on the identification of epitopes that cause antitumor immune responses specific to TAA/LAA. D CAR-T or -NK cells are genetically engineered cells designed to express CARs targeting TAA/LAA on tumor cells. CAR immune cells induce apoptosis in tumor cells by releasing cytotoxic molecules such as IFNγ, perforin, and granzymes and activating death receptor pathways (Fas-FasL and TRAIL-DR4). E ICIs inhibit ICPs such as PD-L1, TIGIT, TIM-3, and CTLA-4, which tumor cells use to exhaust T cells and avoid detection. By inhibiting these immune checkpoints, T cells can recognize and attack tumor cells. GM-CSF, granulocyte‒macrophage colony‒stimulating factor; GVAX: GM-CSF-transduced tumor cell vaccines; DC: dendritic cell; TAA: tumor-associated antigen; LAA: leukemia-associated antigen; MHC: major histocompatibility complex; CAR: chimeric antigen receptor; FasL: Fas ligand; TRAIL: Tumor necrosis factor (TNF)-related apoptosis-inducing ligand; DR: death receptor; ICIs: Immune checkpoint inhibitors; ICPs: immune checkpoint proteins; PD-1: programmed death-1; PD-L1: programmed death-ligand 1; TIM-3: T cell Ig- and mucin-domain-containing molecule-3; TIGIT: T cell immunoreceptor with immunoglobulin and ITIM domain; CTLA-4: Cytotoxic T-lymphocyte-associated protein 4