Table 1.
Summary of Clinical Studies of Inhibitory Receptors
| Targeted Receptor and Focus of Study | Descriptive Findings | Study |
|---|---|---|
| CTLA-4 | ||
| Synovial dendritic cells | Expression and function of CD80 and CD86 costimulator molecules on synovial dendritic cells in chronic arthritis. | Summers K, et al., 1996 |
| T cells | HLA-DR and IL-2R identify persistently activated T cells in psoriasis vulgaris lesional skin: blood and skin comparisons by flow cytometry. | Ferenczi L, et al., 2000 |
| Genetic polymorphisms of CTLA-4 | CTLA-4 polymorphisms in Japanese patients with psoriasis vulgaris. | Tsunemi Y, et al., 2003 |
| Lack of associations of CTLA-4 and ICAM-1 polymorphisms with psoriasis in the Korean population. | Kim Y, et al., 2003 | |
| CTLA-4 gene polymorphisms and natural soluble CTLA-4 protein in psoriasis vulgaris. | Luszczek W, et al., 2006 | |
| Regulatory T cells (Tregs) | Dysfunctional blood and target tissue CD4+CD25high regulatory T cells in psoriasis: mechanism underlying unrestrained pathogenic effector T cell proliferation. | Sugiyama H, et al., 2005 |
| FoxP3 mRNA splice forms in synovial CD4+ T cells in rheumatoid arthritis and psoriatic arthritis. | Ryder L, et al., 2000 | |
| CTLA-4-Ig (Abatacept) | Abatacept in the treatment of patients with psoriatic arthritis: results of a 6-month, multicenter, randomized, double-blind, placebo-controlled, phase II trial. | Mease P, et al., 2011 |
| Inhibition of pro-inflammatory cytokine generation by CTLA-4-Ig in the skin and colon of mice adoptively transplanted with CD45Rhigh CD4+ T cells correlates with suppression of psoriasis and colitis. | Davenport CM, et al., 2002 | |
| Anti-CTLA-4 in cancer therapy | Ipilimumab therapy in patients with advanced melanoma and preexisting autoimmune disorders. | Johnson DB, et al., 2016 |
| 8-methoxypsoralen plus UVA photo chemotherapy (PUVA) | 8-methoxypsoralen plus ultraviolet A therapy acts via inhibition of the IL-23/Th17 axis and induction of Foxp3+ regulatory T cells involving CTLA-4 signaling in a psoriasis-like skin disorder. | Singh TP, et al., 2010 |
| PD-1 | ||
| PD-1 expression | PD-1 signaling in primary T cells. | Riley JL, 2009 |
| Expression of programmed death-1 in skin biopsies of benign inflammatory vs. lymphomatous erythroderma. | Cetinozman F, Jansen PM, Willemze R, 2014 | |
| Analysis of programmed death-1 in patients with psoriatic arthritis. | Peled M, et al., 2015 | |
| PD-1 blockade | PD-1 regulates Imiquimod-induced psoriasiform dermatitis through inhibition of IL-17A expression by innate gamma deltaLow T cells. | Imai Y, et al., 2015 |
| Programmed cell death ligand 1 alleviates psoriatic inflammation by suppressing IL-17A production from programmed cell death 1high T cells. | Kim JH, et al., 2016 | |
| Anti-PD-1 in cancer therapy (Nivolumab and Pembrolizumab) | Exacerbation of psoriasis during nivolumab therapy for metastatic melanoma. | Matsumura N, et al., 2016 |
| Severe psoriasis flare after anti-programmed death ligand 1 (PD-L1) therapy for metastatic non-small cell lung cancer (NSCLC). | Chia PL, John T, 2016 | |
| TIM-3 | ||
| Expression | Impaired expression of Tim-3 on Th17 and Th1 cells in psoriasis. | Kanai Y, et al., 2009 |
| Soluble galactin-9 | Stable form of galectin-9, a Tim-3 ligand, inhibits contact hypersensitivity and psoriatic reactions: a potent therapeutic tool for Th1- and/or Th17-mediated skin inflammation. | Niwa H, et al., 2009 |
| LAG-3 | ||
| No published studies | ||