The largest scale cancer T cell study results published in history

2023-11-21 07:08:15

July 03, 2018 Source: Medical Valley Comprehensive Report

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Lung cancer is called "the king of cancer", and its incidence and mortality are the highest among all cancers, and 85% of lung cancers belong to non-small cell lung cancer. 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 lymphocytes are the key group involved in killing tumor cells, and deeply understand the composition of tumor infiltrating T cells. , lineage and status are important for the development of tumor immunotherapy and the development of effective targets and markers.

Recently, Zhang Zemin, a professor at the School of Life Sciences at Peking University, and the Yan Tiansheng Research Group of Peking University Third Hospital and the BIOPIC Center of the Peking University School of Life Sciences, published a paper entitled "Global characterization of T cells in non-small-cell" in Nature Medicine. Lung cancer by single-cell sequencing, a study that completed the single-cell sequencing of 12,346 T cells from peripheral blood, cancer, and paracancerous tissues of 14 patients with newly diagnosed non-small cell carcinoma. Immunological characteristics of 16 T cell functional subpopulations of small cell lung cancer, tissue distribution characteristics of each subpopulation, and state transition relationships between subpopulations. At the same time, based on T cell-based transcriptome data and T cell receptor (TCR) sequences, the study identified two groups of effector T cells distributed across tissues, and these two groups have potential migration properties, a new immunization The development of therapies provides ideas.

It is understood that this research is the largest cancer T cell study in the world so far. It is worth mentioning that this study also reveals for the first time that there are two CD8+ T cell populations in cancer patients, which may be the state of depleted state T cells. Somatic cells have an important impact on the prognosis of cancer patients.

To fully understand the complex tumor infiltrating T cells in patients with non-small cell lung cancer, the researchers treated 14 patients with lung cancer (including 11 lung adenocarcinomas and 3 squamous cell carcinomas), tumors in vivo, adjacent normal tissues, and peripheral tissues. T cells isolated from blood were subjected to deep single-cell RNA sequencing.

First, after confirming the presence of T lymphocyte infiltration in non-small cell lung cancer, the researchers divided T cells by fluorescence activated cell sorting (FACS) according to T cell surface markers (CD3/CD4/CD8/CD25). Various subtypes. Then, a total of 12,346 cells were sequenced, and the average depth of each cell sequencing was 1.04 million (single-localized sequencing sequence), so that low-expression cytokines and transcription factors were also well detected.

Second, by pedigree tracking (based on T-cell co-expression and T-cell antigen receptors), the researchers found that a significant fraction of effector T cells migrated highly in tissues. In addition to observing depleted state CD8+ T cells in tumor infiltration, the researchers also found two immune cells with depleted T cell precursor cells, the higher the ratio of precursor cells to depleted T cells, lung adenocarcinoma The better the patient's prognosis, the new ideas for lung cancer treatment.

In addition, the researchers also observed that regulatory T cells (Treg) targeting killing of killer immune cells also provide an important idea for immunotherapy. Past studies have generally compared Treg within the tumor as a whole with Treg in adjacent and peripheral blood. The study found that according to the expression of TNFRSF9 (also known as 4-1BB), a group of activated Tregs can be distinguished from lung cancer infiltrating Tregs, and the expression level of inhibitory function-related genes is higher in this group of Treg, suggesting that it is a tumor. Treg cells that truly exert inhibition. At the same time, the proportion of activated Treg is related to the prognosis of patients with lung adenocarcinoma, and can be used as another reliable clinical marker.

Guo Xinyi, a Ph.D. student at the BIOPIC Center of the School of Life Sciences at Peking University, said that the largest single-cell omics study on tumor-related T cells in the world has provided valuable data for subsequent related research work. Resources also lay a solid foundation for a deeper understanding of the immune traits of lung cancer-associated T cells. The scientific findings of this work can guide the clinical classification of lung cancer patients, and also provide new ideas for the patient's precise treatment.

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