Zhao/Jin

Project Title

Target lung microbiota-immune interaction to enhance cancer immunotherapy.

NIH Mentor

Chen Zhao

Penn Mentor

Chengcheng Jin

Project Details

Immune checkpoint inhibitors (ICI) only effective in a minority of patients with lung cancer, which is the leading cause of cancer-related deaths worldwide, and the response appears to depend on the pre-existence of tumor-infiltrating T cells at baseline. Therefore, it is critical to elucidate the mechanisms underlying the lack of anti-tumor T cells in the majority of lung tumors, and devise strategies to convert the “cold” tumors to “hot” tumors, sensitizing them to checkpoint inhibition. The lung is a mucosal tissue colonized by a diverse bacterial community, and pulmonary infections are frequent in lung cancer patients. Our previous work showed lung tumor outgrowth is associated with dysregulated local microbiota, which plays a critical role in promoting inflammation and lung cancer development. Based on our preliminary data, we hypothesize that local microbiota may induce the accumulation of immune-suppressive cells and molecules in the tumor microenvironment (TME), resulting in exclusion and inhibition of anti-tumor T cells. Therefore, the overall goal of this study is to dissect the molecular and cellular mechanisms by which the microbiota shapes the TME and regulates the anti-tumor immunity during lung cancer progression and in response to immunotherapies, and thereby identifying specific bacteria and downstream immune pathways as therapeutic targets to enhance the efficacy of ICI.