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Predicting Response and Outcome of Immunotherapy (IMIT Study)

The arrival of immunotherapy has ushered a new era in cancer treatment, leading to significant and sustained improvement in patient survival. Although checkpoint inhibitors are now regarded pivotal in modern oncology, response rates among patients show inexplicable variation. Our IMIT-project (Immune-Monitoring of Immuno-Therapy) aims at identifying and functionally exploring changes in patients receiving checkpoint inhibitors. In the future, this will help us to tailor individualized therapies for patients by predicting the best response to the growing arsenal of emerging checkpoint inhibitors.

Deciphering the Mechanisms of Toxicity of Immunotherapy

Despite improvement of response rates and survival in several tumor types, there is a potential risk for autoimmune side effects by T-cell infiltration, including skin rash, colitis, pneumonitis, hepatitis, and hypophysitis. As there is evidence of correlation between inflammation in various organs and better response to treatment, we aim to understand the pathogenesis behind these mechanisms. We have recently hypothesized that there may be an association between onset of uveitis and higher response rates in patients with metastatic melanoma (Diem et al., J Immunotherapy, 2016; Nuñez et al., Med. 2023). In patients with non-small cell lung cancer we described a different histologically-dependent T-cell infiltration in skin rash caused by immunotherapy (Hasan Ali et al., Oncoimmunology, 2016). Furthermore, in patients with non-small lung cancer we showed that C reactive protein flare is a non-invasive, easily determined biomarker to predict response to checkpoint inhibitors (Klümper et al., J Immunother Cancer, 2022). 

Identification of previously unknown cancer antigens

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy. However, their use is frequently associated with immune- related adverse events (irAEs) potentially affecting  any  organ.  The  mechanisms  mediating  such irAEs  remain  poorly  understood and biomarkers to predict the development of irAEs are lacking (Berner & Flatz, Immunol Rev, 2023). Therefore, we validated DITAS (discovery of tumor-associated self-antigens) and identified autoreactive napsin-A to be enriched in lung tumors and inflammatory lung lesions during immune checkpoint blockade (Berner et al., Sci. Immunol., 2022). Moreover, we could show that autoimmune toxic effects associated with checkpoint blockade may serve as biomarkers for clinical responses and provide opportunities to identify cancer T-cell targets (Berner et al., JAMA Oncology, 2019). 

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