Literature Express | SCI High Score Literature (IF Value: 19)Biodegradable Nanomissile Targeting the NKG2D/NKG2DL Axis Boosts Photo-Immunotherapy by T Cell Plus NK Cell Attack

Title of the article:

Biodegradable Nanomissile Targeting the NKG2D/NKG2DL Axis Boosts Photo-Immunotherapy by T Cell Plus NK Cell Attack

Downregulation of major histocompatibility complex class I (MHC-I) molecules on tumor cells contributes to an immunosuppressive tumor microenvironment (ITM) by impairing immune recognition via the NKG2D receptor. In this study, we developed a photosensitive, biodegradable nanomissile (PCHM) that mimics natural killer (NK) cell membranes to enhance photo-immunotherapy through coordinated activation of T cells and NK cells. PCHM precisely targets tumor tissues and generates a self-sustained supply of H2O2 and O2, serving as an internal fuel source to amplify photodynamic therapy (PDT). The resulting oxidative stress activates the heat shock protein pathway, upregulating MHC-I expression and promoting antigen presentation through the NKG2D/NKG2DL axis. This triggers a synergistic immune response involving cytotoxic T lymphocytes (CTLs) and NK cells. In addition to inducing immunogenic cell death and cell-membrane immunity, PCHM facilitates remodeling of the ITM. It elicits a robust and durable antitumor immune response capable of eradicating both primary and metastatic tumors. Furthermore, combining PCHM with PD-L1 blockade enhances therapeutic efficacy and prolongs survival. Overall, this work demonstrates the potential of targeting the NKG2D/NKG2DL axis to precisely activate immune responses within tumors, offering an effective strategy to boost PDT and photo-immunotherapy.

Original link:

https://doi.org/10.1002/adfm.202519066

Reference product and cultured cells: FBS-301 MC38 cells