[National Institute of Biomedical Innovation, Health and Nutrition] Elucidation of the mechanism by which neoantigen-specific CD4 T lymphocytes suppress tumor growth
*National Institute of Biomedical Innovation, Health and Nutrition* Press release: September 14, 2024
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Elucidation of the mechanism by which neoantigen-specific CD4 T lymphocytes suppress tumor growth
*Expected for the development of new treatments for cancers that have been difficult to treat*
National Institute of Biomedical Innovation, Health and Nutrition (Ibaraki City, Osaka Prefecture, Chairman: Yusuke Nakamura)
Kazuma Kiyotani Project Leader of the Intractable Disease/Immune Genome Research Project (formerly affiliated with the Cancer Research Foundation, Cancer Precision Medicine Research Center)
The research group led by Immune Genome Analysis Group Leader) is conducting joint research centered on the University of Chicago to develop CD4 cells that specifically recognize neoantigens.
We revealed that T lymphocytes cause changes in stromal cells and suppress tumor growth.
About past research
Tumor tissue is infiltrated by CD8 T lymphocytes called cytotoxic T cells. That CD8
It is known that T lymphocytes find antigens that mark cancer cells and attack them. In recent years, CD4 cells, called helper T cells, T lymphocytes are also known to play an important role in cancer treatment. We have developed CD4 cells that have been genetically introduced with the T lymphocyte receptor (TCR), which binds to cancer landmarks.
We have shown that T lymphocytes exhibit strong tumor growth suppressive effects over a long period of time. However, the detailed mechanism was not yet well understood.
In this research, we used a mouse model to identify neoantigens, which are markers that exist only in cancer cells, and multiple types of TCRs that bind to neoantigens. CD4 with these TCR genes introduced We generated T lymphocytes and investigated their tumor suppression mechanism. Key points of research results
– Created CD4
It has been revealed that T lymphocytes do not directly attack cancer cells, but instead suppress the proliferation of cancer cells by changing the interstitial cells that surround cancer cells. – We discovered that CD4 T lymphocytes, which exhibit long-term tumor suppressive activity in mice, contain multiple types of TCR for a single antigen.
Based on the above results, in addition to cancer immunotherapy using CD8 T lymphocytes, which has attracted attention so far, CD4 T lymphocytes were also found to be important. This is expected to lead to the development of new cancer immune cell therapy, which will become an option for cancers that have been ineffective with conventional treatments.
The results of this research will be published in the international scientific journal “Science Immunology” on September 14, 2024. Website: https://www.science.org/doi/10.1126/sciimmunol.adp6529
*CD8 T lymphocytes*: T cells that express CD8 molecules on the cell surface and are also called cytotoxic T cells or killer T cells. Cells that recognize, attack, and destroy cancer cells and
virus-infected cells.
* CD4 T lymphocytes*: T cells that express CD4 molecules on their cell surface, and many of them act as helper T cells and promote the activity of cytotoxic T cells and B cells.
* Neoantigen * :
It is a new cancer-specific antigen that occurs due to genetic mutations (genetic damage) that occur in cancer cells and does not exist in normal cells. When T cells attack cancer cells, they act as markers for cancer cells.
*Interstitial cells*:
Cells that provide the support structure and environment for living tissues. It is known to help tumor growth and metastasis by
interacting with cancer cells. It consists of macrophages, dendritic cells, and fibroblasts.
Paper information
* Paper title: *
CD4 T cells with convergent TCR recombination reprogram stroma and halt tumor progression in adoptive therapy
* author:*
Steven P. Wolf1,2, Matthias Leisegang1,3,4, Madeline Steiner2, Veronika Wallace2,
Kazuma Kiyotani5,6, Yifei Hu7,8, Leonie Rosenberger3, Jun Huang7,9, Karin Schreiber1,2, Yusuke Nakamura5,6, Andrea Schietinger10, Hans Schreiber1,2,9
1 David and Etta Jonas Center for Cellular Therapy, The University of Chicago, Chicago, USA.
2 Department of Pathology, The University of Chicago, Chicago, USA. 3 Institute of Immunology, Campus Buch, Charite-Universitatsmedizin Berlin, Berlin, Germany.
4 German Cancer Consortium (DKTK), partner site Berlin, and German Cancer Research Center (DKFZ), Heidelberg, Germany.
5 Project for Immunogenomics, Cancer Precision Medicine Center, Japanese Foundation for Cancer Research, Tokyo, Japan.
6 Laboratory of Immunogenomics, Center for Intractable Diseases and ImmunoGenomics (CiDIG), National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Ibaraki-shi, Osaka, Japan.
7 Pritzker School of Molecular Engineering, University of Chicago, Chicago, USA.
8 Pritzker School of Medicine, University of Chicago, Chicago, USA. 9 Committees on Cancer Biology and Immunology and the Cancer Center, The University of Chicago, Chicago, USA.
10 Immunology Program, Memorial Sloan Kettering Cancer Center; New York, USA.
*Published magazine:*
Science Immunology
DOI: 10.1126/sciimmunol.adp6529
*About the Institute of Medical Science, Health and Nutrition* It was established on April 1, 2015 by merging the National Institute of Biomedical Innovation and the National Institute of Health and Nutrition. This research institute is characterized by a wide range of research from medical to health science, and aims to maximize the results of research and development in order to contribute to the sound development of the national economy and other public interests by improving the level of science and technology in Japan. It is positioned as a national research and development agency whose purpose is to secure
Website: https://www.nibiohn.go.jp/
About the University of Chicago
The University of Chicago Medicine & Biological Sciences is one of the nation’s leading academic medical institutions. It comprises the Pritzker School of Medicine, a top medical school in the nation; the University of Chicago Biological Sciences Division; and the University of Chicago Medical Center. Twelve Nobel Prize winners in physiology or medicine have been Affiliated with the University of Chicago Medicine.
Website: https://www.uchicago.edu/
About the Cancer Research Society
The Cancer Research Society was established in 1908 as Japan’s first specialized cancer institution, and has played a leading role in cancer research and treatment in Japan for over 100 years. The Cancer Institute promotes basic cancer research, the Cancer Chemotherapy Center and Cancer Precision Medicine Research Center promote new drug development and cancer genome medicine research, and the creation of new medical treatments. We are home to Cancer Research Ariake Hospital, and together we aim to overcome cancer.
Website: https://www.jfcr.or.jp/
Logo mark (NIBIOHN, University of Chicago, Cancer Research Society)