Tumor immunotherapies such as PD-1 and PD-L1 immune checkpoint inhibitors have had great success in treating advanced or metastatic lung cancer. However, the current standard of care for early-stage lung cancer is still surgery and chemotherapy, so can tumor immunotherapy be used to treat early-stage lung cancer? Recently, researchers at the Mount Sinai School of Medicine have conducted a detailed study of the immune microenvironment of early-stage lung cancer tumors. They found that the immune factors that allow tumor immunotherapy to be successful are already present in the microenvironment of early-stage lung cancer, which means that immunotherapy is promising to be equally successful in patients with early-stage lung cancer. The study was published in the journal Cell. Currently, the common therapies used to treat patients with early-stage lung cancer remain surgical treatment and adjuvant chemotherapy. The 5-year survival rates for patients with early-stage non-small cell lung cancer in stages IA and IB were 83% and 71%, respectively, while those in stage II had a 50% survival rate. This indicates that there is still much room for improvement in the treatment of early-stage lung cancer. Although immune checkpoint inhibitors such as PD-1 or PD-L1 antibodies have shown excellent efficacy in treating advanced lung cancer, they are not being used to treat patients with early-stage lung cancer. One important reason for this is that we do not know the immune status of the microenvironment near early-stage lung cancer tumors. The success of immune checkpoint inhibitors depends on whether immune cells that can kill the tumor are already present around the tumor and whether the anti-cancer ability of these immune cells is inhibited by immune checkpoint proteins such as PD-1 or PD-L1. Therefore, it is important to understand the immune status of the early lung cancer tumor microenvironment. Researchers at Mount Sinai School of Medicine obtained excised tumor tissue, normal lung tissue and blood samples from patients with early-stage lung cancer. They devised a barcoding system that could label all cells in these three different samples with metal isotopes. Mass cytometery by time-of-flight was then used in combination with single cell transcriptomics and multiplex imaging of lung tumors to analyze the immune status of lung tumors in detail at the individual cell level. High-dimensional single-cell profiling of lung cancer tumors at the single-cell level showed that all major immune cell types, most frequently T lymphocytes and mononuclear phagocytes, are clustered around the tumor in the early stages of lung cancer. Regulatory T cells were also already enriched around early tumors. The immune checkpoint proteins PD-1 and PD-L1 have also appeared on the surface of a fraction of CD4+ and CD8+ T lymphocytes and macrophages, respectively. These immune features found in advanced lung cancer were also present in early lung cancer. This means that PD-1 or PD-L1 inhibitors are likely to have the same efficacy in early-stage lung cancer. This study also identified many other new targets for immunotherapy that could significantly increase the number of patients who benefit from immunotherapy. The findings are now being used to help develop clinical trials of immunotherapy for patients with early-stage lung cancer. ”About 50 percent of lung cancer patients have their cancer return after treatment,” said the study’s senior author, Miriam Merad, MD, PhD, professor of oncology science and medicine at Mount Sinai School of Medicine. “Chemotherapy is not very effective when lung cancer is in an advanced stage, so knowing how to killing tumor cells early has a major impact on patient recurrence and eventual survival. Our study demonstrates that immunotherapy is most effective in the early stages of cancer, especially in patients who have never been exposed to chemotherapy.”