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. 2015 Apr 14;4(8):e1026534.
doi: 10.1080/2162402X.2015.1026534. eCollection 2015 Aug.

HHLA2 and TMIGD2: new immunotherapeutic targets of the B7 and CD28 families

Murali Janakiram  1 , Jordan M Chinai  2 , Aimin Zhao  3 , Joseph A Sparano  4 , Xingxing Zang  1
Affiliations

HHLA2 and TMIGD2: new immunotherapeutic targets of the B7 and CD28 families

Murali Janakiram et al. Oncoimmunology. .

Abstract

We and others recently discovered HHLA2 as a new B7 family member and transmembrane and immunoglobulin domain containing 2 (TMIGD2) as one of its receptors. Based on a new study we propose that HHLA2 may represent a novel immunosuppressive mechanism within the tumor microenvironment and hence could be a target for cancer therapy. TMIGD2 may be another therapeutic target.

Keywords: B7 family; CD28 family; HHLA2; TMIGD2; angiogenesis; immunosuppression; immunotherapy; ligand; receptor; tumor microenvironment.

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Figures

Figure 1.
Figure 1.
The B7 and CD28 families and the significance of HHLA2 and TMIGD2 within the tumor microenvironment. (A) A structural representation of the B7 and CD28 family members. (B) A proposed model for the roles of HHLA2 and TMIGD2 within the tumor microenvironment. Tumor-expressed HHLA2 can interact not only with an unidentified receptor on activated T cells that leads to coinhibition, but also with TMIGD2 on endothelium that stimulates tumor angiogenesis. Additionally, tumor-expressed HHLA2 can bind to other immune cells and likely affects their functions in ways that are not yet understood. Finally, tumor-associated macrophages (TAM) may express HHLA2 and interact with TMIGD2 on endothelium.
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