Recent Advances in ADAM17 Research: A Promising Target for Cancer and Inflammation

Table 2

Substrates implicated in tumor immunosurveillance.

Substrate	Tumor immunosurveillance
MHC class I-related chain A and B protein [21, 22, 161]	Costimulator of cytokine production. Triggers cytotoxic effector activity of natural killer cells and certain T cell subsets. Immune escape if shed
FcγRIIIA (CD16) [25, 26]	Prevention of shedding improves NK cell and improves antibody-dependent cellular toxicity (ADCC) of rituximab
Tim-3 [29, 162]	Blocking with monoclonal antibodies and posterior stimulation with TLR results in an increase in the production of IL-12, IL-6, and IL-10, but a reduced expression of PD-1, an inhibitor molecule of the T cell function [30]
	Treatment with antibody specific to TIM-3 exacerbated experimental autoimmune encephalomyelitis (EAE) in mice and increased the proliferation and activation of macrophages [31]
PMEL17 [33]	Patients with metastatic melanoma immunized with the gp100:209–217 (210 M) followed by high-dose interleukin 2 lead to a better response rate than interleukin 2 alone [34]
GP100 [32]
CD154 [35, 163]	Injection of adenovirus CD154-established tumors produced sustained tumor regression in the majority of tumor-carrying mice. CD154 gene transfer elicited a tumor-specific cytolytic T-lymphocyte response that suppressed the growth of established lung carcinoma in the presence of IFNγ [36]
Interleukin 23 receptors [42]	Genetic deletion or antibody-mediated elimination of IL-23 leads to increased infiltration of cytotoxic T cells rendering a protective effect against chemically induced carcinogenesis. Transplanted tumors are growth-restricted in hosts depleted for IL-23 or in IL-23-receptor-deficient mice [44]
4-1BB [46]	Agonists can both potentiate antitumor and antiviral immunity, while at the same time ameliorating autoimmune disease [164]
	Preclinical data with agonist, SA-4-1BBL, mediates stimulation for tumor immunotherapy [45]