This study will help us to understand the mediators of EMT-associated immunosuppression and whether this immunosuppression contributes to the drug resistance and metastases known to be associated with EMT.
—Yanyan Lou, MD, PhD
Yanyan Lou, MD, PhD, a hematology/oncology fellow at The University of Texas MD Anderson Cancer Center, is the recipient of the very first 2014 Conquer Cancer Foundation of ASCO Young Investigator Award (YIA), generously supported by the Women Who Conquer Cancer.
After receiving her medical degree from Henan Medical University in China, Dr. Lou completed her doctorate degree in oncology at West China University of Medical Sciences and an internal medicine residency at UT Southwestern in Austin.
“My personal experience with my grandfather who died from lung cancer first stimulated my desire to pursue a career in cancer medicine. Driven by a passion for developing new cancer therapies, I entered medical school and then graduate school where I received structured training in translational research with a specific focus on cancer immunotherapy,” said Dr. Lou.
YIA Research Project
Dr. Lou received a 2014 YIA for her project “Investigating tumor microenvironment immune phenotypes in epithelial-mesenchymal transition and EGFR tyrosine kinase inhibitor-resistant NSCLC: Implication for immunotherapy.” She is comentored by John Heymach, MD, PhD (2003 YIA, 2004 CDA) and Patrick Hwu, MD.
Epithelial-mesenchymal transition (EMT) is a key process that drives cancer metastases. Data have demonstrated that EMT in non–small cell lung carcinoma (NSCLC) is associated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor resistance independent of EGFR mutation status. Furthermore, preliminary data demonstrate that both EMT and EGFR tyrosine kinase inhibitor resistance are highly associated with upregulated programmed cell death 1 ligand (PD-L1), a key immune checkpoint molecule inducing immunosuppression. PD-1 and its ligand PD-L1 have emerged as a critical inhibitory pathway that regulates T cell response and maintains immunosuppression in tumor microenvironment.
Based on these findings, Dr. Lou hypothesizes that EMT and EGFR tyrosine kinase inhibitor resistance are associated with an immunosuppressive phenotype in tumor microenvironment and targeting this immune suppression will potentially inhibit metastases and reduce tumor growth in EGFR tyrosine kinase inhibitor–resistant NSCLC.
Potential Impact for Patients
Lung cancer is the leading cause of cancer death in the United States. Although identification of mutations and development of EGFR tyrosine kinase inhibitor have led to an evolution of treatment in NSCLC, all such treated patients will eventually acquire resistance despite an initial response.
According to Dr. Lou, “This study will help us to understand the mediators of EMT-associated immunosuppression and whether this immunosuppression contributes to the drug resistance and metastases known to be associated with EMT. Importantly, it will potentially identify the biomarkers for selecting which patients benefit from PD-1/PD-L1 blockade and establish a rationale mechanistic basis for combining PD-L1 blockade with targeted agents.”
Women Who Conquer Cancer
The Conquer Cancer Foundation’s Women Who Conquer Cancer campaign brings together women from across the country to fund promising careers and outstanding research through the Young Investigator Award (YIA).
Interested in learning more about Women Who Conquer Cancer? Visit www.conquercancerfoundation.org/wwcc. ■
© 2014. American Society of Clinical Oncology. All rights reserved.