Tradition chemotherapy in lung cancer treatment had its limit, but recent immunotherapy with CTLA-4 antibody had showed the promising future of immunotherapy in lung cancer treatment. Beside the heterogeneous characteristic of lung cancer, tumor induced immune suppression is another important factor for tumor progression and metastasis. Human cancer could induce several suppressor cells, including Treg and myeloid-derived suppressor cells (MDSC), and cause the normal cytotoxic T cells, NK cells and dendritic cell dysfunction. In our report had proved that monocytic MDSC could suppress T cells proliferation, and the amount of MDSC is inversely correlated with treatment response and progress free survival of chemotherapy. However, the interaction between MDSC and other immune cells in lung cancer patient is still unclear. Chemotherapy is the backbone of cancer treatment, and some chemotherapy could induce immunogenic cell death (ICD), which could augment the antigen presenting cells and cause tumor cell death. However, chemotherapy also cause cell necrosis, and cause releasing of damage associated molecular pattern (DAMP), such as S100A9, and cause MDSC accumulation. Thus it is important to clarify whether some chemotherapy could induce more ICD but not DAMP, and make treatment more effective. This 3 years project is to test the hypothesis. We will enroll 180 lung cancer subjects and collect pre- and post-chemotherapy PBMC and serum to identify the difference of DAMP and ICD between chemotherapies. MDSC and other immune cells will be isolated from PBMC and co-culture with cancer cell line in vitro. Co-culture system could verify the interaction of MDSC and other immune cells to the cancer cells. Pharmacological inhibitors, stimulators, and over-expression will be used to confirmed the candidate target. Gene expressionmicroarrays and chip-on-ChIP will be used to study the genes affected at the global level. This study will not only advance our knowledge into the mechanism whereby abnormal immune change of lung cancer patients, but also will possibly provide new biomarkers and a novel therapeutic direction for developing effective therapy for lung cancer.
|Effective start/end date||8/1/13 → 7/31/14|
- Lung cancer
- Myeloid derived suppressor cells
- Immunogenic cell death
- Damage-associated molecular pattern