Chen Zhao, M.D.

Lung cancer is the leading cause of cancer-related mortality worldwide. Although immune checkpoint inhibitors have shown encouraging results in the treatment of lung adenocarcinoma, the response rate and overall survival are still low, especially in patients with low PD-L1 expression in the tumor site. Existing evidence suggests that interactions involving lung cancer cells, microbes, and immune cells in the tumor microenvironment affect tumor progression and patients’ responses to treatments. Therefore, the discovery of new therapeutic targets and more effective immunotherapies requires a deeper understanding of these complex interactions, especially in the tissue context rather than as isolated elements. However, traditional investigation methods, such as flow cytometry and low-plex histology, lack the ability to measure cells, mediators, and the microbiota simultaneously while also collecting critical spatial information.

To address this gap in our knowledge, we have been using advanced multiplex, multimode, two-dimensional (2D), and three-dimensional (3D) imaging techniques, together with spatial-transcriptomic analysis, to investigate these complex interactions in the tumor microenvironment. We collaborate with Dr. Chengcheng Jin at the University of Pennsylvania and have shown that commensal microbiota promote lung cancer development via gamma-delta T cells.

Taking advantage of these techniques and the translational research opportunities at CCR, we are studying the composition and spatial changes of the lung microbiota during lung cancer development as well as the interactions between lung microbiota and immune cells in patients with lung cancer. We developed a novel spatial meta-transcriptomic analysis method and revealed the spatial distribution of the intratumor microbiome in lung cancer. The findings of our laboratory findings are brought back to patients as the first clinical trial targeting the intratumor microbiome, "Study of Aerosolized Antibiotics and Pembrolizumab in Advanced Non-small Cell Lung Cancer"(NCT05777603).

Dr. Zhao received his M.D. from the combined eight-year program at Tsinghua University and Peking Union Medical College in 2011. After graduation, he studied gene regulation of glucose metabolism with Drs. Raimund Herzog and Robert Sherwin at Yale School of Medicine. Then Dr. Zhao did his internal medicine residency at Mount Sinai St. Luke’s-Roosevelt Hospital, and developed a strong interest in tumor immunology during his oncology rotations at Memorial Sloan Kettering Cancer Center. He started his hematology and oncology fellowship at the National Institutes of Health in 2016 and joined Dr. Ronald Germain’s research group at the National Institute of Allergy and Infectious Diseases. Dr. Zhao has been focusing on using advanced imaging techniques to investigate the tumor-immune microenvironment in lung cancer. He received the ASCO Young Investigator Award and the SITC-AstraZeneca Immunotherapy in Lung Cancer (Early Stage NSCLC) Clinical Fellowship Award. In 2019, Dr. Zhao joined the Thoracic and GI Malignancies Branch at the NCI Center for Cancer Research as an Assistant Clinical Investigator. He became a Stadtman Investigator in 2023. Dr. Zhao received the NIH Bench-to-Bedside and Back Program (BtB) award in 2020 for "Target Lung Microbiota-Immune Interaction to Enhance Cancer Immunotherapy". His team developed a spatial meta-transcriptomic analysis method and revealed the spatial distribution of the intratumor microbiome in 2022. In 2023, Dr. Zhao brought the laboratory findings to the first clinical trial perturbing intratumor microbiome in patients, "Study of Aerosolized Antibiotics and Pembrolizumab in Advanced Non-small Cell Lung Cancer" (NCT05777603), which was further supported by ASCO Career Development Award.