Lung cancer, 85% of which are non-small cell lung cancer (NSCLC), is by far the leading cause of cancer-related death, making up almost 25% of all cancer deaths. Considering the complexity of the tumor microenvironment, single-cell transcriptome sequencing technology has been widely used in the research of tumor-infiltrating immune cells in recent years. T cells, also called T lymphocytes, are important tumor-killing cells in the tumor microenvironment, functioning as the key element of cancer immunotherapy. A deep understanding of the composition, lineage and functional status of tumor-infiltrating T cells is of great significance to the development of immunotherapies including effective targets and the prediction of their clinical responses in cancers.

One research paper titled "Global characterization of T cells in non-small-cell lung cancer by single-cell sequencing" was published on June 25, 2018 by Nature Medicine (IF=32.621), which provided significant biological findings about tumor-infiltrating T cells in NSCLC by the collaboration of teams leading by Zemin Zhang from Peking University BIOPIC, Beijing Advanced Innovation Center for Genomics, and Peking University -Tsinghua Center for Life Sciences, Tiansheng Yan from Department of Thoracic Surgery of Peking University Third Hospital, and Bayer AG.

In this study, the authors performed deep single-cell RNA sequencing for 12,346 T cells from 14 NSCLC patients. They detected 16 heterogeneous T cell subsets with distinct gene expression profiles and functional properties, and depicted their features of tissue distribution, clonal expansion, state transition and cross-tissue migration in NSCLC based on the T cell transcription data and the T cell receptor (TCR) sequence. In addition, they revealed two clusters of inter-tissue effector T cells with a highly migratory nature, which provides information for the development of new immunotherapy.

CD8 T cells in the tumor microenvironment will reach a dysfunctional state called "exhaustion" due to long-term antigen stimulation. This study detected exhausted cells in tumors of NSCLC patients, and also found two clusters of tumor-infiltrating CD8+ T cells exhibiting states preceding exhaustion that might transit into exhausted T cells. Moreover, the ratio of "pre-exhausted" T cells to exhausted T cells is related to the prognosis of patients with lung adenocarcinoma, which provides new clinical markers for lung adenocarcinoma.

Targeting regulatory T cells (Tregs) that inhibit effector cells is also an important strategy for immunotherapy. Tregs in the tumor microenvironment are usually used as a homogenous compartment to compare with those in the adjacent and peripheral blood in previous studies. However, this study found a subset of activated Tregs exhibiting a higher level of suppression-related gene expression within the tumor Tregs. Furthermore, the proportion of such activated Tregs is related to the prognosis of patients with lung adenocarcinoma, indicating that signature of activated tumor Tregs can be used as reliable clinical marker.

Xinyi Guo, a PhD student at BIOPIC of Peking University and the first author of this paper, said that this work is one of the largest single-cell omics studies of tumor-related T cells in NSCLC, providing extremely valuable data for subsequent related researches. In addition, the scientific findings of this work provide a reliable basis for a deeper understanding of the immune characteristics of tumor-infiltrating T cells in lung cancer, which can guide the clinical classification of lung cancer patients and provide new ideas for precise cancer treatment.

In addition to Xinyi Guo, the first authors of this study include Yuanyuan Zhang, a PhD student at School of Life Sciences, Chunhong Zheng, a postdoctoral fellow at Center for Life Sciences, Liangtao Zheng, a PhD student at Academy for Advanced Interdisciplinary Studies of Peking University, and Jintao Song, a physician in thoracic surgery at Peking University Third Hospital. Zemin Zhang from Peking University BIOPIC, Beijing Advanced Innovation Center for Genomics, and Peking University -Tsinghua Center for Life Sciences, and Tiansheng Yan from Department of Thoracic Surgery of Peking University Third Hospital, are the co-corresponding authors. This research was funded by the Peking University-Bayer Strategic Cooperation, Beijing Advanced Innovation Center for Genomics, National Key Research and Development Program, National Natural Science Foundation of China, and Peking University-Tsinghua Life Sciences.