Tumor microenvironment and immune therapy of non-small cell lung cancer
The tumor-stroma crosstalk network especially the immune-related regulations in cancer development has also been a great interest for lab study. We have made efforts to systematically dissect the microenvironmental heterogeneity of lung adenocarcinomas, and provide cellular and molecular landscapes that contribute to carcinogenesis. While we have been profiling the transcriptome of stromal and tumor epithelial compartments from fresh clinical specimens and a mouse model of KrasG12Dp53-/- tumors, signaling that impacts on anti-tumor immunity are investigated. 1) Using tumor vaccine strategies to study the development of tumor-specific cytotoxic T cells in NSCLC. We have established a tumor vaccine model by using irradiated whole tumor cells or tumor neoantigen peptides. We found that the short-term but not persistent exposure to tumor antigens could efficiently evoke anti-tumor immunity in the host, which is mediated by CD64L+CD44- memory T cells. Further characterization of the differentiation pathway of the tumor-specific T cells is undergoing. 2) Exploring the synergic effect of radiation therapy (RT) and immune checkpoint inhibition (ICI) in NSCLC. RT in combination with anti-PD1 represents a promising regimen in NSCLC treatment. However, the mechanisms underlying the efficacy of combination therapy requires investigation. In cooperation with Drs. Altorki and Mittal, we found a new mechanism by which RT-activated of lung epithelium acted as a mediator of the immunomodulatory to enhance ICI. This has provided another clue that the microenvironment factors would significantly impact the development of anti-tumor immunity.