Intra‐Operative Definition of Glioma Infiltrative Margins by Visualizing Immunosuppressive Tumor‐Associated Macrophages

Abstract

Accurate delineation of glioma infiltrative margins remains a challenge due to the low density of cancer cells in these regions. Here, a hierarchical imaging strategy to define glioma margins by locating the immunosuppressive tumor‐associated macrophages (TAMs) is proposed. A pH ratiometric fluorescent probe CP2‐M that targets immunosuppressive TAMs by binding to mannose receptor (CD206) is developed, and it subsequently senses the acidic phagosomal lumen, resulting in a remarkable fluorescence enhancement. With assistance of CP2‐M, glioma xenografts in mouse models with a tumor‐to‐background ratio exceeding 3.0 for up to 6 h are successfully visualized. Furthermore, by intra‐operatively mapping the pH distribution of exposed tissue after craniotomy, the glioma allograft in rat models is precisely excised. The overall survival of rat models significantly surpasses that achieved using clinically employed fluorescent probes. This work presents a novel strategy for locating glioma margins, thereby improving surgical outcomes for tumors with infiltrative characteristics.

ScRNA-seq reveals novel immune-suppressive T cells and investigates CMV-TCR-T cells cytotoxicity against GBM

“…Given that FXYD6 is also expressed in some normal cells, such as stromal cells and oligodendrocytes, the direct target inhibition of FXYD6 may influence the physiological function of normal cells and lead to certain side effects. Bipositive TAMs and M2-TAMs cells studied by Cao et al 39 have similar effects, used the feature of accumulation at the margins of GBM and designed to outline the tumor margins and guide the surgery, thereby improving surgical prognosis. However, the production of both bipositive TAMs and FXYD6 was regulated by CMV infection.…”