Reprogramming　the　immunosuppressive　tumor　microenvironment　(TME)　to　boost　CD8+　T　cell　infiltration　is　crucial　for　anti-tumor　immunotherapy.　In　this　study,　a　bionic　nanoplatform　(VGRM)　based　on　a　two-dimensional　vanadium　carbide　(MXene)　carrying　glucose　oxidase　(GOx)　and　CRISPR/Cas9　was　constructed,　which　enabled　a　cascade　reaction　that　amplified　the　generation　of　reactive　oxygen　species　(ROS)　while　depleting　glutathione　(GSH)　by　combining　MXenzyme　and　natural　enzymes.　The　CRISPR/Cas9　system　could　reduce　the　expression　of　MTH1,　depress　tumor　cells’　self-defense　against　oxidative　stress　and　thus　significantly　enhance　the　therapeutic　effect　of　ROS.　Additionally,　the　excellent　NIR-II　photothermal　performance　endowed　VGRM　with　photoacoustic　imaging　(PA)　and　photothermal　therapy　(PTT)　capabilities.　The　enhanced　oxidative　stress　and　photothermal　killing　ability　could　activate　the　cGAS/STING　innate　immune　pathway,　induce　immunogenic　cell　death　(ICD),　and　at　the　same　time　reverse　the　immunosuppressive　TME,　which　promoted　CD8+　T　cells　infiltration,　and　thereby　inhibiting　tumor　proliferation.　Meanwhile,　antigen-activated　memory　T　cells　(adaptive　immunity)　could　suppress　tumor　recurrence　and　metastasis　effectively.　This　study　provides　a　novel　strategy　for　the　combined　application　of　MXene　and　gene　editing　therapy　in　modulating　the　tumor　immune　microenvironment.　©　2025