Understanding and therapeutically harnessing the tumor-supportive and immune-suppressive functions of TRAIL and CD95L in SCLC (C06)

• Subject Area: Immunology ; Hematology, Oncology ; Cell Biology
• Term: since 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 413326622

G. Liccardi and H. Walczak will capitalize on their findings made in the first funding period showing survival extension of RP mice (SCLC GEMM) treated with TRAIL or CD95L (FasL) blockers. The significant therapeutic advantage offered by this approach will now be extended to a more immunogenic GEMM of SCLC, the RPM model, in which there is an increased tumor mutational burden and which has been developed by A01 in the context of this CRC. They will study to which extent the therapeutic effects observed with inhibition of TRAIL or CD95L depend on tumor cell-intrinsic versus -extrinsic effects, respectively, within the context of such models. Additionally, they will study whether inhibiting TRAIL and/or CD95L synergizes with ICI in SCLC mouse models with increased neoantigenicity. Moreover, in collaboration with C05/C08 they will determine whether death ligand blockade, with or without ICI, may also synergize with mRNA-based neoantigen-targeting vaccines in the RPM model.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1399: Mechanisms of drug sensitivity and resistance in small cell lung cancer
• Applicant Institution: Universität zu Köln
• Project Heads: Dr. Gianmaria Liccardi, since 7/2023; Professor Henning Walczak, Ph.D.