CD274 at a glance

CD274 / PD-L1 (programmed death ligand-1), also known as B7-H1, is one of the most important members of the B7 family of regulatory proteins. Unlike costimulatory receptors B7-1 and B7-2 (CD80 and CD86), this molecule gives to the T cells mainly inhibitory signals. Interaction between CD274 and its receptor CD279 (PD1) regulates the balance between stimulatory and inhibitory signals to T cells, and hence also the balance between immunity and autoimmunity. Its function is very important e.g. in case of chronic viral and bacterial infections, when the delicate balance between efficient immune defence and immune-mediated tissue damage is essential. CD274 is expressed mainly on dendritic cells, activated monocytes and activated T cells. Its high expression was demonstrated in the heart, placenta, skeletal muscle and lung tissue, and weaker expression in the thymus, kidney, spleen, and liver.
 
Ability of CD274 to suppress T cell functions, unfortunately, is utilized by many cancers to evade immune system. This 40 kDa glycoprotein is expressed by various carcinomas of the lung, digestive tract, ovaries, bladder, breast, as well as by melanomas or gliomas. Their CD274 tolerizes tumor-reactive T cells, promotes the development and maintenance of induced Treg cells, and leads to tumor resistance to cytotoxic T cell attack. CD274 expression in tumors is associated with larger tumor size, greater metastasis, poor survival, and higher recurrence rate. Even pathogens (e.g. Schistosoma) may exploit CD274 to evade an immune response.
 
One of potent inducers of CD274 expression is IFN-γ. This fact represents a serious problem in case of those immunotherapies, that rely on stimulation of cytotoxic anticancer immunity, where IFN-γ plays key roles. Fortunately, when a cell-based cancer vaccine contains enough costimulatory molecules, its effect overcomes tumor-protective role of CD274. Even soluble CD80-IgG1 Fc fusion protein can restore anti-tumor T cell functions suppressed by CD274.
 
CD274 expression can be also monitored on antigen presenting cells to predict effect of PD1 inhibitor therapy. In this case the lower is pretherapeutic CD274 expression on blood dendritic cells and monocytes, the better seems to be the prognosis of the therapy. Combination of CD274 monitoring on cancer cells and on antigen presenting cells, together with targeting CD274 functions and affecting related signaling cascades may represent a possibly promissing approach. However, this topic is still under intensive research.
 
 Fig. 1: Schematic image of CD274 glycoprotein.
 
 

The mouse monoclonal antibody 29E.2A3 recognizes an extracellular epitope of human CD274.

Applications: FC, IHC(F), FUNC (blocking)

Available formats:

 

Fig. 2: Separation of human monocytes (red-filled) from lymphocytes (black-dashed) in flow cytometry analysis (surface staining) of human PHA stimulated peripheral blood mononuclear cells stained using anti-human CD274 (29E.2A3) PerCP-Cy5.5 antibody (4 μl reagent per milion cells in 100 μl of cell suspension).
 
 
Further reading:
 
Butte MJ, Keir ME, Phamduy TB, Sharpe AH, Freeman GJ: Programmed death-1 ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responses. Immunity. 2007 Jul;27(1):111-22.
 
Fang X, Chen C, Xia F, Yu Z, Zhang Y, Zhang F, Gu H, Wan J, Zhang X, Weng W, Zhang CC, Chen GQ, Liang A, Xie L, Zheng J: CD274 promotes cell cycle entry of leukemia-initiating cells through JNK/Cyclin D2 signaling. J Hematol Oncol. 2016 Nov 17;9(1):124.
 
Cao Y, Zhang L, Ritprajak P, Tsushima F, Youngnak-Piboonratanakit P, Kamimura Y, Hashiguchi M, Azuma M: Immunoregulatory molecule B7-H1 (CD274) contributes to skin carcinogenesis. Cancer Res. 2011 Jul 15;71(14):4737-41.
 
Wilcox RA, Feldman AL, Wada DA, Yang ZZ, Comfere NI, Dong H, Kwon ED, Novak AJ, Markovic SN, Pittelkow MR, Witzig TE, Ansell SM: B7-H1 (PD-L1, CD274) suppresses host immunity in T-cell lymphoproliferative disorders. Blood. 2009 Sep 3;114(10):2149-58.
 
Haile ST, Bosch JJ, Agu NI, Zeender AM, Somasundaram P, Srivastava MK, Britting S, Wolf JB, Ksander BR, Ostrand-Rosenberg S: Tumor cell programmed death ligand 1-mediated T cell suppression is overcome by coexpression of CD80. J Immunol. 2011 Jun 15;186(12):6822-9.
 
Haile ST, Dalal SP, Clements V, Tamada K, Ostrand-Rosenberg S: Soluble CD80 restores T cell activation and overcomes tumor cell programmed death ligand 1-mediated immune suppression. J Immunol. 2013 Sep 1;191(5):2829-36.
 
Riemann D, Schütte W, Turzer S, Seliger B, Möller M: High PD-L1/CD274 expression of monocytes and blood dendritic cells is a risk factor in lung cancer patients undergoing treatment with PD1 inhibitor therapy. Cancers (Basel). 2020 Oct 13;12(10):2966.
 
Alexander PG, McMillan DC, Park JH: A meta-analysis of CD274 (PD-L1) assessment and prognosis in colorectal cancer and its role in predicting response to anti-PD-1 therapy. Crit Rev Oncol Hematol. 2021 Jan;157:103147.

 

READ ALSO our older blog, concerning CD279 (PD-1), which is receptor for PD-L1 ligand (CD274), in clinical practice HERE


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