期刊
NATURE REVIEWS DRUG DISCOVERY
卷 14, 期 8, 页码 561-584出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nrd4591
关键词
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资金
- Claudia Adams Barr Program for Innovative Cancer Research
- American Association for Cancer Research [14-40-01-MAHO]
- American Society of Clinical Oncology
- Kidney Cancer Association
- [P50CA101942]
- [U54CA163125]
- [P01AI054456]
- [R01AI089955]
- NATIONAL CANCER INSTITUTE [P50CA101942, U54CA163125] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI089955, P01AI054456] Funding Source: NIH RePORTER
Targeting immune checkpoints such as programmed cell death protein 1 (PD1), programmed cell death 1 ligand 1 (PDL1) and cytotoxic T lymphocyte antigen 4 (CTLA4) has achieved noteworthy benefit in multiple cancers by blocking immunoinhibitory signals and enabling patients to produce an effective antitumour response. Inhibitors of CTLA4, PD1 or PDL1 administered as single agents have resulted in durable tumour regression in some patients, and combinations of PD1 and CTLA4 inhibitors may enhance antitumour benefit. Numerous additional immunomodulatory pathways as well as inhibitory factors expressed or secreted by myeloid and stromal cells in the tumour microenvironment are potential targets for synergizing with immune checkpoint blockade. Given the breadth of potential targets in the immune system, critical questions to address include which combinations should move forward in development and which patients will benefit from these treatments. This Review discusses the leading drug targets that are expressed on tumour cells and in the tumour microenvironment that allow enhancement of the antitumour immune response.
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