The Effect and Mechanisms of Chemotherapy in Recruit Inflammatory Cells into Tumor Microenvironment of Lung Cancer Patients

Lung cancer remains the leading cause of cancer death worldwide. Emerging evidence suggests that, in addition to genetic/metabolic changes of the tumor itself, tumor microenvironments play a crucial role in tumor initiation and progression, as well as in mediating drug resistance. We have reported that increasing circulating CD14+S100A9+ MDSC is correlated with poor treatment response of chemotherapy and shorter progression-free survival. The clinical importance of MDSCs recruiting to tumor microenvironment needed to be evaluate. This 3-year project is aim to study the mechanisms of tumor recruiting S100A9+ MDSC to tumor site. In the first year, we will use the trans-well co-culture system and proteomic/microarray analysis to study the possible mechanisms of recruitment of S100A9+ MDSC to tumor site by using different lung cancer cell lines. To identify possible up-regulation receptors and pathways involving in the different type of cancer cells. In second year, animal model of MDSC migration in the cancer bearing mice will be established. The interaction between MDSCs and cancer cells will be confirmed. In the third year, we will validate the finding of previous study from patient serum and PBMC. Mediators and intracellular signals will be investigated. Parellel to the in vitro study, clincial relevance of chemotherapy and MDSC will be studied in an observational clinical study. Results from this study will help us gain insight into mechanisms of tumor recruitment of MDSC, and the effects of chemotherapy to MDSC. Potentially, novel treatments targeting those cells or related signals could be considered as effective anticancer strategy in the future.