December 9^th 2025, Cologne

Paper on "ERBB2 signaling drives immune cell evasion and resistance against immunotherapy in small cell lung cancer" by MSSO fellows Lydia Meder, Charlotte Orschel and Cyrielle Bouchez has now been published. All three MSSO fellows contributed equally to this work - remarkable: C. Orschel as MD student. Claudia Orschel, David Stahl, Filippo Beleggia and Johannes Brägelmann also contributed to this work. 

Small cell lung cancer (SCLC) is a particularly aggressive form of lung cancer, accounting for about 15% of all lung cancer cases. In most patients, the disease is already advanced at the time of diagnosis. Although treatment is often effective initially, the tumors quickly become resistant and survival is very limited. An important reason for this is that SCLC cells hide from the immune system.
In our study, we examined tumor samples from patients and mouse models. We found that SCLC cells in metastases often lose an important “distinguishing marker” – the so-called MHC-I molecule. Without this molecule, immune cells cannot recognize and attack the cancer cells.
We were able to show that, among others, a specific signaling pathway in SCLC cancer cells, the so-called ERBB2 signaling pathway, is responsible for this. It suppresses MHC-I in tumor cells, enabling them to escape the immune system. Blocking this signaling pathway allows the tumor cells to restore MHC-I. This makes them visible to the immune system and allows the tumor to be targeted. The combination of ERBB2 blockade with immunotherapy (PD-1 blockade) proved particularly promising in our preclinical testing, achieving particularly strong and sustained antitumor effects in our models. These results suggest that this combination therapy could represent a new treatment strategy for patients with SCLC in the future.

Publication:
Meder, L., Orschel, C.I., Bouchez, C.L. et al. ERBB2 signaling drives immune cell evasion and resistance against immunotherapy in small cell lung cancer. Nat Commun (2025)