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Coinhibitory Receptor Expression and Immune Checkpoint Blockade: Maintaining a Balance in CD8+ T Cell Responses to Chronic Viral Infections and Cancer
- Source :
- Frontiers in Immunology, Vol 8 (2017)
- Publication Year :
- 2017
- Publisher :
- Frontiers Media SA, 2017.
-
Abstract
- In cancer and chronic viral infections, T cells are exposed to persistent antigen stimulation. This results in expression of multiple inhibitory receptors also called “immune checkpoints” by T cells. Although these inhibitory receptors under normal conditions maintain self-tolerance and prevent immunopathology, their sustained expression deteriorates T cell function: a phenomenon called exhaustion. Recent advances in cancer immunotherapy involve blockade of cytotoxic T lymphocyte antigen-4 and programmed cell death 1 in order to reverse T cell exhaustion and reinvigorate immunity, which has translated to dramatic clinical remission in many cases of metastatic melanoma and lung cancer. With the paucity of therapeutic vaccines against chronic infections such as HIV, HPV, hepatitis B, and hepatitis C, such adjunct checkpoint blockade strategies are required including the blockade of other inhibitory receptors such as T cell immunoreceptor with immunoglobulin (Ig) and immunoreceptor tyrosine-based inhibitory motif domains, T cell Ig and mucin-domain containing-3, lymphocyte activation gene 3, and V-domain Ig-containing suppressor of T cell activation. The nature of different chronic viral infections and cancers is likely to influence the level, composition, and pattern of inhibitory receptors expressed by responding T cells. This will have implications for checkpoint antibody blockade strategies employed for treating tumors and chronic viral infections. Here, we review recent advances that provide a clearer insight into the role of coinhibitory receptor expression in T cell exhaustion and reveal novel antibody-blockade therapeutic targets for chronic viral infections and cancer. Understanding the mechanism of T cell exhaustion in response to chronic virus infections and cancer as well as the nature of restored T cell responses will contribute to further improvement of immune checkpoint blockade strategies.
- Subjects :
- lcsh:Immunologic diseases. Allergy
0301 basic medicine
medicine.medical_treatment
Receptor expression
T cell
Immunology
Biology
03 medical and health sciences
Immune system
Cancer immunotherapy
medicine
cancer
Cytotoxic T cell
Immunology and Allergy
T cell exhaustion
chronic infections
Immunotherapy
immune checkpoints
Immune checkpoint
3. Good health
Blockade
030104 developmental biology
medicine.anatomical_structure
checkpoint blockade
immunotherapy
lcsh:RC581-607
Subjects
Details
- Language :
- English
- ISSN :
- 16643224
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- Frontiers in Immunology
- Accession number :
- edsair.doi.dedup.....bdfabb8fd49e1d96a01827ebdf5b1c08
- Full Text :
- https://doi.org/10.3389/fimmu.2017.01215