Ultrathin MnO ₂ ‐PEG‐PD‐L1 Nanosheets Enable Tumor Microenvironment Modulation and NIR‐II Photothermal Immunotherapy for Durable Control of Lung Cancer and Postoperative Recurrence

Lung cancer is one of the most common and deadly malignancies worldwide. Although immune checkpoint inhibitors, including PD‐1/PD‐L1 blockers, have benefited a subset of patients, response rates remain limited, and recurrence is frequent because of the immunosuppressive tumor microenvironment (TME), characterized by hypoxia and dysregulated reactive oxygen species (ROS). Here, we develop ultrathin MnO 2 ‐PEG‐PD‐L1 nanosheets that integrate TME regulation and PD‐L1‐targeted delivery for 1064 nm NIR‐II photothermal‐enhanced immunotherapy of lung cancer. MnO 2 ‐PEG‐PD‐L1 exhibits efficient photothermal conversion and controlled degradation in acidic, H 2 O 2 ‐rich conditions, scavenging H 2 O 2 , alleviating hypoxia, and downregulating the HIF‐1α/adenosine axis to relieve A2AR‐associated immunosuppression. In vitro, PD‐L1 modification enhances uptake by LLC cells, and MnO 2 ‐PEG‐PD‐L1 plus photothermal treatment induces hallmark immunogenic cell death, including HMGB1 release, CRT exposure, ATP secretion, and maturation of bone marrow‐derived dendritic cells in coculture. In a murine LLC tumor model, MnO 2 ‐PEG‐PD‐L1 with NIR‐II irradiation markedly suppresses tumor growth, reduces Ki67‐positive cells, achieves a high tumor inhibition rate, and prolongs survival without significant body‐weight loss. Immune analyses show that this treatment remodels the TME by decreasing neutrophils, Th17 cells, and pro‐inflammatory cytokines. In a postoperative recurrence model, MnO 2 ‐PEG‐PD‐L1 combined with photothermal therapy effectively delays recurrent tumor growth and improves postoperative survival, indicating durable T cell‐mediated antitumor responses and long‐term control of recurrence. This nanosheet platform offers a promising strategy for integrated TME modulation and NIR‐II photothermal immunotherapy against refractory lung cancer.