The team at Peking University revealed dynamic changes in colorectal t cells.

On October 29, Zhang Zemin Research Group of Beijing University's High-Precision Innovation Center for Future Genetic Diagnostics (ICG), BIOPIC of the School of Life Sciences, Peking University-Tsinghua Joint Center for Life Sciences, and The Ouyang Wenjun Team of Anjin Corporation of the United States and Shen Zhanlong Of Peking University People's Hospital, published the latest research results.
this study developed startRAC's bioinformatics analysis method, which systematically depicts the tissue distribution characteristics, cloning hyperpluses, migration and state transformation relationships of a large number of T cells from 12 colorectal cancer patients (Figure 1), which is the most comprehensive and in-depth novel study on the size of a single T cell in a colorectal cancer microenvironment in the world to date.
, the study found new groups of CD4-positive T-cells with differences between patients with microsatellite instable (MSI) and microsatellite stabilization (MSS), and functionally explained the synergistic stimulus factors of the specific expression of the new group.
this world-leading ground-breaking work that provides ideas for the study of T cells in other diseases and the development of new treatment options.
study was published in the journal Nature, a leading international magazine, under the title "Lineage tracking reveals dynamics of the relationships of T cells in colorectal cancer".
tumor-immersed T lymphocytes play a central role in tumor immunotherapy.
inhibitor drugs developed based on immunocheckpoints (e.g. CTLA-4, PD-1/PD-L1) have achieved good results in a variety of cancer treatments, but different types of cancer patients have very different efficacy.
recent mouse model experiments have shown that T cells outside the tumor can participate in systemic anti-tumor immune response, and the therapeutic effect of CD8-T cells in different states on immunocheckpoint inhibitors is significantly different, suggesting that T-cell migration potential and state change characteristics may play a vital role in its fight against tumors.
research based on single-cell transcription alsome has made a series of progress in the subtype classification and molecular mapping of T cells, and it has been difficult to depict the dynamic changes of T cells in human body.
to overcome the difficulties of this research, Professor Zhang Zemin's research team pioneered the use of T cell receptors (TCR) as a label, developed STARTRAC systematic quantitative analysis of biological information, using this method to colorectal cancer patients cancerous tissue, cancer-side tissue and peripheral blood identified 20 types of different types of T-cells, and made a series of new progress.
research has found that, in addition to the tumor microenvironment, TCR also affects the transformation of tumor-immersed CD8-effect memory T cells to "exhausted T cell" and effect T cells, a finding that will help us understand the source of depleted T cells in the tumor microenvironment and provide new ideas for reversing their state.
several clinical trials have shown that patients with MSI/dMMR (mismatched to repair genetic defects) colorectal cancer patients respond significantly better than MSS patients to the treatment of immunocheckpoint inhibitors.
previous tissue-based studies have found significant differences in gene expression in these two types of colorectal cancer patients, such as IFNG and PDCD1, presumably from CD8 T cells and TH1 cells.
the search and identification of difference groups in MSI and MSS colorectal cancer patients has not been resolved due to technical limitations.
the study, based on single-cell sequencing techniques, found that MSS colorectal cancer patients were significantly richer than MSI patients with TH17 cells, while MSI patients significantly enriched a group of highly expressed CXCL13 TH1cells.
notable, the researchers found two groups of high-expression IFNG CD4 TH1-like cells in colorectal cancer tissue, and only the high-expression CXCL13 subgroup was significantly rich in MSI patients.
the researchers further found that these two groups of TH1-like cells have different IFNG transcription regulatory factors, in which BHLHE40 not only promotes the effect of IFN-ɣ molecules, but also inhibits the production of inhibitory IL-10 molecules, suggesting that CXCL13-TH1-cells may be related to the therapeutic inhibitor response of immune checkpoints (Figure 3).
, these group cells highly express a variety of membrane surface proteins with unknown function in tumor immunity, of which IGFLR1 as a new synergetic stimulation factor, and IGFLR1/IGFL3 pathways as potential drug treatment targets. Zhang Lei, a postdoctoral fellow at the Frontier Cross Research Institute at Peking University,
the first author of the study, said that the current international research on T cells in the tumor microenvironment pays more attention to the classification level, and it is urgent to make a breakthrough in the urgent need for novel analytical perspectives and concepts.
the research team has pioneered the development of STARTRAC systematic bioinformatics quantitative analysis method based on TCR sequence, which deeply depicts the dynamic changes of T cells in the microenvironment of colorectal cancer tumors, which provides a solid foundation for further analyzing the differences between T cells in different colorectal cancer patients, and provides an opportunity to tap new therapeutic targets.
Zhang Lei, postdoctoral fellow at the Frontier Cross Research Institute of Peking University, Yu Xin of the Department of Inflammation and Oncology of Amincorporation, Zheng Liangtao, Ph.D. student at the Frontier Cross Research Institute of Peking University, and Zhang Yuanyuan, ph.dinal student of The School of Life Sciences of Peking University, were the first authors of the paper.
BIOPIC of Peking University School of Life Sciences, Beijing Future Genetic Diagnostics High-Precision Innovation Center (ICG), Zhang Zemin of The Peking University-Tsinghua Joint Center for Life Sciences, Ouyang Wenjun of the Department of Inflammation and Oncology of Amgen Corporation of the United States, and Shen Zhanlong of Gastroenterology Surgery at Peking University People's Hospital as co-authors of this paper.
the research was supported and funded by the Beijing Future Gene DiagnosticS Center for High-Excellence Innovation (ICG), the National Key Research and Development Program, the National Natural Science Foundation of China and AMGEN of the United States.
Source: Department of Scientific Research, Peking University.