The PD-1 / PDL-1 Pathway

PD-1 Pathway: The Immune System Stoplight

PD-1 Pathway: The Immune System Stoplight

The immune system fights off pathogens, but this defensive force can be pathogenic itself when hyperactive, resulting in autoimmune diseases such as lupus and multiple sclerosis. Consequently, the body has developed multiple mechanisms to suppress the immune system when necessary.

One method of immunosuppression is the PD-1 pathway. This pathway is activated in response to the mobilization of the immune system. The receptor PD-1 is expressed on the surface of activated lymphocytes. Similarly, its ligand, PD-L1, is expressed by antigen-presenting cells in response to cytokine signaling. When PD-L1 is bound to PD-1, downstream signaling undoes the phosphorylation events associated with activation, thereby reverting lymphocytes to an inactive state [1, 2].

Antibody Cat no. Type Applications
PD-1/CD279 Antibody 18106-1-AP Rabbit Poly ELISA, WB, FC, IHC

 

IHC of paraffin-embedded human ovary tumor tissue slide using PD-1/CD279 Antibody,at dilution of 1:200 (under 10x lens).

Immunotherapy: A Promising Treatment for Cancer

Tumor cells take advantage of the PD-1 pathway to evade the immune system [3]. Consequently, many pharmaceutical companies have been developing drugs to inhibit PD-1 and PD-L1. In clinical trials, many patients have shown strong responses to these therapies [4-10]. For these drugs to be most effective, a high number of CD8+ T cells must already be at the tumor site, ready to be mobilized after inhibition of the PD-1 pathway [11].Recent investigations have uncovered promising methods of increasing the efficacy of PD1 inhibitors. One method is combining PD1 inhibitors with other drugs, such as HDAC inhibitors [12] and anti-CTLA4 antibodies [9]. Another method is using biomarkers to predict response to therapy [13,14]. Recent work has also suggested that GSK3 inhibitors can enhance effects of immunotherapy [15].Though these results have been encouraging, several challenges remain, including the mitigation of autoimmune effects and how to overcome drug resistance.

Related Products

Antibody Cat no. Type Applications
PD-L1/CD274  66248-1-Ig Mouse mono  ELISA, WB, IHC, IF, FC
CD86/CTLA 4  13395-1-AP  Rabbit poly  ELISA, WB, FC
CD3 epsilon  17617-1-AP  Rabbit poly  ELISA, WB, IHC, IP, FC
GSK3B  22104-1-AP  Rabbit poly  ELISA, WB, IHC, IF, IP
BRAF  20899-1-AP  Rabbit poly  ELISA, IHC, IF, 

ELISA Kits

Human PD-L1 ELISA Kit
Catalog number:  KE00074
KE00074 is a solid phase sandwich Enzyme Linked-Immuno-Sorbent Assay (Sandwich ELISA). The PD-L1 ELISA kit is to be used to detect and quantify protein levels of endogenous PD-L1. 
Tests: Reacted Species:
1 X 96 well plate Human
Sample type: Sensitivity:
Serum, Plasma, Cell culture supernatant,Cell lysate 0.04 ng/mL
Range: Assay Type:
0.156 ng/mL-10 ng/mL Sandwich
Human PD1 ELISA Kit
Catalog number: KE00075

KE00075 is a solid phase sandwich Enzyme Linked-Immuno-Sorbent Assay (Sandwich ELISA). The PD1 ELISA kit is to be used to detect and quantify protein levels of endogenous PD1.

Tests: Reacted Species:
1 X 96 well plate Human
Sample type: Sensitivity:
Serum, Plasma, Cell culture supernatant,Cell lysate 43 pg/mL
Range: Assay Type:
125 pg/mL-8000 pg/mL Sandwich

References

1. Ohegbulam et al. (2015) Human cancer immunotherapy with antibodies to the PD-1 and PD-L1 pathway. Trends Mol Med. 21:24-33.2. Haanen, J. (2013) Immunotherapy of Melanoma. EJC Suppl 11:97-105.3. Yao et al. (2013) Advances in targeting cell surface signaling molecules for immune modulation. Nat Rev Drug Discov. 12:130-146.4. Topalian, S. et al. (2012) Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N. Engl. J. Med. 366:2443-2454.5. Hamid, O. et al. (2013) Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N. Engl. J. Med. 369:134-144.6. Topalian, S. L. et al. (2012) Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N. Engl. J. Med. 366:2443–24547. Brahmer, J. R. et al. (2012) Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N. Engl. J. Med. 366:2455–24658. Hamid, O. et al. (2013) Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N. Engl. J. Med. 369:134–1449. Wolchok, J. D. et al. (2013) Nivolumab plus ipilimumab in advanced melanoma. N. Engl. J. Med. 369:122–13310. Topalian, S. L. et al. (2014) Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J. Clin. Oncol. 32:1020–1030 11. Tumeh, P. et al. (2014) PD-1 blockade induces responses by inhibiting adaptive immune response. Nature. 515:568-71.

12. Woods, D. et al. (2015) HDAC inhibition upregulates PD-1 ligands in melanoma and augments immunotherapy with PD-1 blockade. Cancer Immunol Res 12:1375-85.

13. Chakravarti, N., & Prieto, V. G. (2015). Predictive factors of activity of anti-programmed death-1/programmed death ligand-1 drugs: immunohistochemistry analysis. Translational Lung Cancer Research, 4:743–751.

14. Barak, V. et al. (2015) Assessing response to new treatments and prognosis in melanoma patients, by the biomarker S-100B. Anticancer Res. 35:6755-60.

15. Taylor, A. et al. (2014) Glycogen synthase kinase 3 inactivation drives T-bet-mediated downregulation of co-receptor PD-1 to enhance CD8+ cytolytic T cell responses. Immunity 44:274-86.

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Posted:
27 October, 2016

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