Application of PD-1 Blockade in Cancer Immunotherapy

The programmed cell death protein 1 (PD-1) pathway has received considerable attention due to its role in eliciting the immune checkpoint response of T cells, resulting in tumor cells capable of evading immune surveillance and being highly refractory to conventional chemotherapy. Application of anti...

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Vydané v:	Computational and structural biotechnology journal Ročník 17; s. 661 - 674
Hlavní autori:	Wu, Xiaomo, Gu, Zhongkai, Chen, Yang, Chen, Borui, Chen, Wei, Weng, Liqiang, Liu, Xiaolong
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	Netherlands Elsevier B.V 01.01.2019 Research Network of Computational and Structural Biotechnology Elsevier
Predmet:	antibodies biotechnology Checkpoint blockade clinical trials commercialization drug therapy immune evasion Immune surveillance immunosuppression Immunotherapy monitoring neoplasm cells neoplasms patients PD-1 PD-L1 programmed cell death Review T-lymphocytes cTnI PTPs CXCL9 PMBCL IHC ITT PTEN MHC HR UC NF-κB DNMT PI3K Immunotherapy PFS TIM3 B2M JMJD3 LAG3 cHL DOR 5-AZA-dC HCC PKC SIRPα ITIM GEJ DCM ZAP70 TGF RCC CRC LCK HNSCC PD-1 MSI-H ASCT MAP ERK TCR TIICs DZNep ORR AEs NFAT IFN SHP2 BV DCs PD-L1 CTLA-4 GC ICOS Checkpoint blockade ADCC IrAEs dMMR CC SCLC APCs AP1 NSCLC OS VEGF ITSM ICC TMB BICR Immune surveillance MCC TME BATF PRC2 TILs EZH2 TGF, Transforming growth factor PKC, Protein kinase C AP1, Activator protein 1 MAP, Mitogen-activated protein LAG3, Lymphocyte-activation gene 3 HR, Hazard ratio BV, Brentuximab vedotin DOR, Duration overall response SIRPα, Signal-regulatory protein alpha DCs, Dendritic cells HCC, Hepatocellular carcinoma JMJD3, Jumonji Domain-Containing Protein 3 PMBCL, Primary mediastinal large B-cell lymphoma NFAT, Nuclear factor of activated T cells DZNep, 3-Deazaneplanocin A ICC, Investigator-choice chemotherapy ITSM, Immune-receptortyrosine-based switch motif NF-κB, Nuclear factor-κB dMMR, DNA mismatch repair deficiency SCLC, Small cell lung cancer PFS, Progression-free survival cTnI, Cardiac troponin I TMB, Tumor mutation burden ICOS, Inducible T-cell co-stimulator TIM3, T-cell immunoglobulin and mucin-domain containing-3 BATF, Basic leucine zipper transcriptional factor ATF-like ITIM, Immune-receptortyrosine-based inhibitory motif PD-L1, Programmed death-ligand 1 PTPs, Protein tyrosine phosphatases MSI-H, Microsatellite instability-high TME, Tumor microenvironment ERK, Extracellular signal–regulated kinase ITT, Intention-to-treat ZAP70, Zeta-chain-associated protein kinase 70 TCR, T-cell receptor B2M, β2 microglobulin OS, Overall survival ADCC, Antibody-dependent cellular cytotoxicity BICR, Blinded Independent Central Review CTLA-4, Cytotoxic T-lymphocyte–associated antigen 4 PD-1, Programmed cell death 1 cHL, Classical Hodgkin lymphoma DCM, Dilated cardiomyopathy NSCLC, Non-small cell lung cancer 5-AZA-dC, 5-aza-2′-deoxycytidine EZH2, Enhancer of zeste homolog 2 HNSCC, Head and neck squamous cell carcinoma CC, Cervical cancer ORR, Overall response rate GC, Gastric cancer PRC2, Polycomb repressive complex 2 RCC, Renal cell carcinoma TIICs, Tumor infiltrating immune cells PTEN, Phosphatase and tensin homolog ASCT, Autologous stem cell transplantation APCs, Antigen presenting cells IHC, Immunohistochemistry LCK, Tyrosine-protein kinase Lck VEGF, Vascular endothelial growth factor GEJ, GASTRIC or gastroesophageal junction PI3K, Phosphoinositide 3-kinase SHP2, Src homology 2 domain-containing phosphatase 2 CXCL9, C-X-C motif chemokine ligand 9 IFN, Interferon IrAEs, Immune related adverse events DNMT, DNA methyltransferase AEs, Adverse events MCC, Merkel cell carcinoma MHC, Major histocompatibility TILs, Tumor-infiltrating lymphocytes UC, Urothelial carcinoma CRC, Colorectal cancer
ISSN:	2001-0370, 2001-0370
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Shrnutí:	The programmed cell death protein 1 (PD-1) pathway has received considerable attention due to its role in eliciting the immune checkpoint response of T cells, resulting in tumor cells capable of evading immune surveillance and being highly refractory to conventional chemotherapy. Application of anti-PD-1/PD-L1 antibodies as checkpoint inhibitors is rapidly becoming a promising therapeutic approach in treating tumors, and some of them have successfully been commercialized in the past few years. However, not all patients show complete responses and adverse events have been noted, suggesting a better understanding of PD-1 pathway mediated immunosuppression is needed to predict patient response and improve treatment efficacy. Here, we review the progresses on the studies of the mechanistic role of PD-1 pathway in the tumor immune evasion, recent clinical development and commercialization of PD-1 pathway inhibitors, the toxicities associated with PD-1 blockade observed in clinical trials as well as how to improve therapeutic efficacy and safety of cancer immunotherapy. [Display omitted]
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 ObjectType-Review-3 content type line 23
ISSN:	2001-0370 2001-0370
DOI:	10.1016/j.csbj.2019.03.006