期刊
FRONTIERS IN IMMUNOLOGY
卷 12, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2021.752042
关键词
immune reconstitution; thymus; immunotherapy; TCR repertoire diversity; T cells
类别
资金
- Amy Strelzer Manasevit Research Program
- Italian Association for Cancer Research (AIRC) [21147]
- Italian Ministry of Health
- Ministero dell'Istruzione, dell'Universita e della Ricerca [2017 WC8499_ 004]
- Ministero della Salute [RF-20 16-02364388]
The recognition and immune response against tumor antigens by T cells depends on the diversity of the T-cell receptor (TCR) repertoire, which can be impaired by immunological insults and aging-related decline in thymus function. Manipulating thymic function to enhance anti-tumor immunity is crucial in improving response to cancer immunotherapy, especially checkpoint blockade therapy. The limited response rate to checkpoint blockade therapy may be linked to suboptimal TCR repertoire in cancer patients prior to therapy.
The capacity of T cells to recognize and mount an immune response against tumor antigens depends on the large diversity of the T-cell receptor (TCR) repertoire generated in the thymus during the process of T-cell development. However, this process is dramatically impaired by immunological insults, such as that caused by cytoreductive cancer therapies and infections, and by the physiological decline of thymic function with age. Defective thymic function and a skewed TCR repertoire can have significant clinical consequences. The presence of an adequate pool of T cells capable of recognizing specific tumor antigens is a prerequisite for the success of cancer immunotherapy using checkpoint blockade therapy. However, while this approach has improved the chances of survival of patients with different types of cancer, a large proportion of them do not respond. The limited response rate to checkpoint blockade therapy may be linked to a suboptimal TCR repertoire in cancer patients prior to therapy. Here, we focus on the role of the thymus in shaping the T-cell pool in health and disease, discuss how the TCR repertoire influences patients' response to checkpoint blockade therapy and highlight approaches able to manipulate thymic function to enhance anti-tumor immunity.
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