Immuno-editing via programmed cell death in SCLC (A05)

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

S. v. Karstedt and her team will address the question of how evolution of SCLC is shaped by adaptive immunity-mediated selection before clinical presentation. In the first funding period, they established a key role for extrinsic modes of cell death in shaping differentiation-associated selection of SCLC and identified ferroptosis as a novel vulnerability of non-neuroendocrine SCLC. Furthermore, they found that caspase-8 loss aggravates metastasis formation by favoring a tumor-protective microenvironment and demonstrated that loss of the adaptive immune system is permissive for tumor formation and affords outgrowth of tumors with more immunogenic mutations. As part of the second funding period, they aim to mechanistically how metabolic changes in neuroendocrine SCLC dictates ferroptosis resistance. Moreover, they will address the question how lack of immunoediting shapes the cell of origin pool and molecular subtype in SCLC.

• 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 Head: Professorin Dr. Silvia von Karstedt