Analysis of the Microenvironment of Lung Cancer and Exploration of the Mechanism of Resistance to Immunotherapy

Lung cancer is a highly heterogeneous disease. Cancer cells and cells within the tumor microenvironment together determine disease progression, as well as response to or escape from treatment. Tumor ecosystems are comprised of cancer cells, infiltrating immune cells, stromal cells, and other cell types together with noncellular tissue components, which interact and collectively determine disease progression as well as response to therapy. It is well known that cancer patients elicit very individualized responses to different treatments, demanding better characterization of the whole tumor ecosystem beyond currently applied clinical typing of somatic mutations in cancer cells.

Immune checkpoint blockers (ICBs) have revolutionized the management of patients with lung cancer. Blocking the interaction between the programmed cell death protein 1 (PD-1) receptor and its primary ligand (PD-L1) has demonstrated remarkable anticancer activity, and anti-PD-1/PD-L1 drugs have been approved both as single agents or in combination with cytotoxic chemotherapy. However, most patients receiving anti-PD-1/PD-L1 monoclonal antibodies do not derive benefit. Hence, there is a crucial need to identify reliable predictive biomarkers of the response to anti-PD-1/PD-L1 agents to develop precision medicine for NSCLC immunotherapy as well as to identify novel mechanisms underlying resistance to ICBs.

To map the cell type-specific landscape of cancer cells and their tumor microenvironment in lung cancer, the investigators plan to conduct a multiomics analysis（such as, Genomics, proteomics, single cell RNA sequencing, space transcriptomics）of tumor tissue and blood, aiming at analyzing tumor heterogeneity, mapping the microenvironment map of lung cancer and exploring the mechanism of sensitivity and resistance to anti-PD1/PD-L1 antibodies.