This project aims to unravel the mechanisms of resistance to transferrin receptor–targeted internal radiotherapy (RIV-Tf) in lung cancer. RIV-Tf may combine localized cytotoxic effects with a potential modulation of the tumor microenvironment, offering a promising thera(g)nostic strategy. Preliminary data show significant tumor reduction without complete remission, suggesting adaptive resistance mechanisms. The project integrates transcriptomic analyses enabled by a microfluidic platform developed at LICB and various biological techniques (flow cytometry, ELISA, western blot, targeted imaging) to identify molecular and immunological signatures associated with treatment response. These signatures will be validated in vivo to guide rational therapeutic combinations. Conducted jointly by the ImmunoMaps and LICB teams at CEA, this multidisciplinary work will deepen our understanding of the interplay between radiobiology and tumor immunity and help optimize RIV efficacy in oncology.