P11 - Molecular mechanisms of immune response and exhaustion in male and female smokers, ex-smokers and never-smokers with lung cancer
Antibodies against the immune checkpoint protein programmed cell death protein 1 (PD-1) and its ligand PD-L1 have greatly improved the treatment of lung cancer and other solid organ tumours. However, responses to these medications are not ubiquitous, and patients whose tumours do initially respond often go on to develop recurrence or progression. PD-1 expression, smoking history and gender appear to affect the efficacy of checkpoint inhibitors. Immune exhaustion is also thought to play a role in treatment failure in this setting, and is a current target for novel drug development.
The aim of this doctoral thesis project is to further study the role of immune exhaustion in lung cancer, with a particular focus on immune exhaustion in subgroups defined by gender and by smoking history. Clinical phenotypes and immune cell populations will be correlated with molecular features of tumor and lymph nodes as well as with clinical outcomes. We hypothesize that the antitumoral immune response varies between current smokers, former smokers and never-smokers, as well as between male and female patients. Understanding these differences may lead to novel individualization strategies in the perioperative and palliative use of checkpoint inhibitors.
Within this project we will expand current NSCLC patient cohorts to include deep clinical phenotyping and prospective biomaterials archiving including detailed smoking histories, alloimmunization history (eg. parity, blood products) and blood for biomarker analysis. We will then complete morphological assessments and multiplex staining of tumour (center vs. invasive margin), peritumoral lung tissue and regional lymph nodes, including lymph nodes not directly infiltrated by tumour cells, in subgroups of surgical and non-surgical patients defined by smoking status, gender and exposure to checkpoint inhibitor therapies.
Prof. Dr. med. Amanda Tufman, MD, B.Sc.Department of Pneumology University Hospital of Munich Ziemssenstr. 1/5 80336 München +49 89 4400 5 2590 |