Seminar to outline CRISPR screens in KRAS-driven lung cancer immunotherapy resistance
A seminar will present work on KRAS-driven lung cancer and immunotherapy resistance. The research uses immune-competent mouse models and CRISPR-Cas9 screens to identify targets that sensitise tumour cells to T cell-mediated killing.
Immunotherapy has revolutionised the treatment of lung cancer patients, however, durable response rates are low. Lung cancers that harbour concurrent mutations in KRAS, STK11(LKB1) and KEAP1 fail to derive benefit from PD(L)-1 inhibition alone. A greater understanding of the cell-intrinsic processes that allow these tumours to evade immune detection is required to enhance therapeutic outcomes.
In a seminar, Kate Sutherland will share the progress her laboratory has made in understanding the biology of KRAS-driven lung cancer using immune-competent preclinical mouse models that recapitulate the human disease. She will discuss how these models were combined with unbiased whole genome CRISPR-Cas9 co-culture screens to identify gene targets that sensitise Kras/Stk11/Keap1-altered lung cancer cells to T cell-mediated killing.
Deciphering the molecular mechanisms that underpin immune-sensitisation by these novel immunotherapeutic targets holds the key to achieving more effective therapy responses for patients.
Her research program has made major contributions to understanding the molecular mechanisms that underpin heterogeneity in lung cancer. Earlier work generated tools that led to the identification of the cells-of-origin of three main subtypes of lung cancer.