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Review
. 2015 Nov 11;5(4):e1113367.
doi: 10.1080/2162402X.2015.1113367. eCollection 2016 Apr.

CD137 and CD137L signals are main drivers of type 1, cell-mediated immune responses

Bhushan Dharmadhikari  1 , Meihui Wu  1 , Nur Sharalyn Abdullah  1 , Sakthi Rajendran  1 , Nur Diana Ishak  1 , Emily Nickles  1 , Zulkarnain Harfuddin  2 , Herbert Schwarz  2
Affiliations
Review

CD137 and CD137L signals are main drivers of type 1, cell-mediated immune responses

Bhushan Dharmadhikari et al. Oncoimmunology. .

Abstract

CD137 is expressed on activated T cells and NK cells, among others, and is a potent co-stimulator of antitumor immune responses. CD137 ligand (CD137L) is expressed by antigen presenting cells (APC), and CD137L reverse signaling into APC enhances their activity. CD137-CD137L interactions as main driver of type 1, cell-mediated immune responses explains the puzzling observation that CD137 agonists which enhance antitumor immune responses also ameliorate autoimmune diseases. Upon co-stimulation by CD137, Th1 CD4+ T cells together with Tc1 CD8+ T cells and NK cells inhibit other T cell subsets, thereby promoting antitumor responses and mitigating non-type 1 auto-immune diseases.

Keywords: CD137; T cell polarization; Tc1; Th1.

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Figures

Figure 1.
Figure 1.
Schematic representation of bidirectional signal transduction for the CD137 receptor/ligand system and its effects on antigen presenting cells (APC), T cells and natural killer (NK) cells.
Figure 2.
Figure 2.
The effects of agonistic anti-CD137 antibodies on type 1 polarization which promotes (green arrows) anticancer immune responses and inhibits (red lines) type 2-mediated autoimmune reactions.
Figure 3.
Figure 3.
The effects of inhibition of CD137–CD137L interaction by antagonistic anti-CD137 or anti-CD137L antibodies on the bidirectional signal transduction for the CD137 receptor/ligand system is depicted exemplary for the case of an APC–T cell interaction.
See this image and copyright information in PMC

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