期刊
GENE
卷 638, 期 -, 页码 20-25出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.gene.2017.09.050
关键词
Human Programmed Cell Death I (hPD-I) gene; Immune-checkpoint inhibition; Immunotherapy; Hyperprogressive disease status
资金
- NIDA/FDA [P50 DA036107]
- AA MDSIF [146818]
- American Cancer Society [124171-IRG-13-043-02]
- Pennsylvania State University College of Medicine
Anti-PD-1 therapy is a novel immune-checkpoint inhibition therapy with tremendous potential in treating refractory/relapsed cancers. The 20 year journey of human PD-1 research went through 3 phases: 1) discovering PD-1 gene structure and genomic organization, 2) understanding the mechanism of PD-1 mediated immune checkpoint regulatory effects in coordination with its ligands (PD-Ll and L2), 3) and translating our knowledge of PD-1 gene into a robust clinical anticancer approach by targeting the PD-1 immune-checkpoint pathway. The success of human PD-1 gene study reflects the advancement and trends of modern biomedical research from the laboratory to the bedside. However, our journey of understanding the PD-1 gene is not yet complete. Clinical investigation data show a high variety of response rates among different types of cancers to PD-1 immune checkpoint inhibition therapy, with a range of 18% to 87%. There is no reliable biomarker to predict an individual patient's response to PD-1 inhibitory immunotherapy. Patients can present with primary, adaptive, or even acquired resistance to PD-1 immune-checkpoint inhibition therapy. Furthermore, the emerging data demonstrates that certain patients experience hyperprogressive disease status after receiving PD-1 immune checkpoint inhibition therapy. In conclusion, PD-1 immune-checkpoint inhibition therapy has opened up a new venue of advanced cancer immunotherapy. Meanwhile, further efforts are still warranted in both basic scientific mechanism studies and clinical investigation using the principles of personalized and precision medicine.
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