2021 LCRF-AstraZeneca Research Grant
Lingtao Jin, PhD
University of Texas Health Science at San Antonio
Targeting tumor-immune microenvironment to improve durvalumab efficacy in small cell lung cancer
Small cell lung cancer that accounts for around 15% of lung cancer cases is the most aggressive subtype of lung cancer with a five-year survival rate of less than 5%. The results of numerous clinical trials have been disappointing and, and as a result, treatment options for small cell lung cancer have not had the same progress as non-small cell lung cancer. Anti-PD-L1 immunotherapy such as durvalumab has recently received FDA approval as a first line therapy for small cell lung cancer. This approval is an important advance for patients with small cell lung cancer, whose treatment strategies and clinical outcomes had remained unchanged for more than three decades. Compared with chemotherapy alone, however, adding anti-PD-L1 therapy only moderately extends patient survival. Such modest efficacy of immunotherapy in small cell lung cancer highlights the unmet need for more effective combination therapy approaches.
To investigate how anti-tumor immunity is suppressed in small cell lung cancer, Dr. Jin’s lab explored that tumor-derived exosomes, a small vehicle released by cancer cells that contain lipids, proteins, sugars, etc, may play a critical role in suppressing anti-tumor immunity. Further analysis revealed that these tumor-derived exosomes contain a large quantity of lipids, which can compromise the function of dendritic cells, a type of immune cells that play a key role in facilitating anti-tumor immunity. Therefore, Dr. Jin’s lab will further evaluate whether blocking tumor-derived exosome-induced dendritic cell suppression could be used to boost anti-tumor immunity and improve the efficacy of durvalumab in small cell lung cancer.