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What leads to the exhaustion of immune cells in the tumor microenvironment?

No. 43c | 09/08/2021 | by Koh

Guoliang Cui, of the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), receives one of the 2021 Lloyd J. Old STAR Awards providing a grant of $1.25 million. Guoliang Cui is studying the mechanisms of T cell exhaustion in the context of cancer.

Guoliang Cui
© DKFZ/Jung

The Cancer Research Institute, a US nonprofit organization, is dedicated to harnessing our immune system's power to control and potentially cure all types of cancer. Cancer Research Institute funds the most innovative clinical and laboratory research around the world, supports the next generation of the field's leaders, and serves as the trusted source of information on immunotherapy for cancer patients and their caregivers.

This year's funding activity of CRI includes six Lloyd J. Old STAR Awards. Each award provides a grant of $1.25 million over 5 years to future "stars" in the field of cancer immunology to support exploration of unconventional, high-risk/high-reward research directions that have significant potential to advance cancer immunotherapeutics.

CD8+ T cells play essential roles in fighting against cancer. However, CD8+ T cells frequently become functionally impaired or "exhausted" in the tumor microenvironment. Exhausted CD8+ T cells are characterized by increased expression of inhibitory receptors and decreased secretion of effector cytokines. Exhausted CD8+ T cells also have metabolic defects.

T cell exhaustion is a major hurdle that currently limits the efficacy of immunotherapeutic regimens. Despite extensive research efforts, the mechanisms regulating exhausted T cell differentiation and dysfunction remain incompletely understood.

Guoliang Cui's research program focuses on the elucidation of the molecular mechanisms through which anti-tumor T cells become exhausted. His laboratory plans to use genetically engineered mouse models, immunostimulatory metabolites, and molecular biology techniques to understand the mechanisms regulating CD8+ T cell exhaustion in the tumor microenvironment.

The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) with its more than 3,000 employees is the largest biomedical research institution in Germany. More than 1,300 scientists at the DKFZ investigate how cancer develops, identify cancer risk factors and search for new strategies to prevent people from developing cancer. They are developing new methods to diagnose tumors more precisely and treat cancer patients more successfully. The DKFZ's Cancer Information Service (KID) provides patients, interested citizens and experts with individual answers to all questions on cancer.

Jointly with partners from the university hospitals, the DKFZ operates the National Center for Tumor Diseases (NCT) in Heidelberg and Dresden, and the Hopp Children's Cancer Center KiTZ in Heidelberg. In the German Consortium for Translational Cancer Research (DKTK), one of the six German Centers for Health Research, the DKFZ maintains translational centers at seven university partner locations. NCT and DKTK sites combine excellent university medicine with the high-profile research of the DKFZ. They contribute to the endeavor of transferring promising approaches from cancer research to the clinic and thus improving the chances of cancer patients.

The DKFZ is 90 percent financed by the Federal Ministry of Education and Research and 10 percent by the state of Baden-Württemberg. The DKFZ is a member of the Helmholtz Association of German Research Centers.

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