Targeting T Cell Co-receptors for Cancer Therapy

Callahan, Margaret K.; Postow, Michael A.; Wolchok, Jedd D.

doi:10.1016/j.immuni.2016.04.023

Cited by 425 publications

(362 citation statements)

References 72 publications

Supporting

Mentioning

351

Contrasting

Unclassified

Order By: Relevance

“…Although promising, we have learned from the studies in solid tumors that clinical response to anti-PD-1 is only about 18–40%. 42 Tumors may use a variety of inhibitory pathways to evade immune attack. Combinational treatment targeting multiple suppressive mechanisms is an attractive strategy to improve cancer immunotherapy.…”

Section: Discussionmentioning

confidence: 99%

VISTA is highly expressed on MDSCs and mediates an inhibition of T cell response in patients with AML

et al. 2018

View full text Add to dashboard Cite

Treatment of acute myeloid leukemia (AML) remains challenging. Enhancement of anti-tumor responses by blocking negative immune regulators is a promising strategy for novel effective leukemia therapeutics. V-domain Ig suppressor of T-cell activation (VISTA) is a recently defined negative regulator mediating immune evasion in cancer. To investigate the effect of VISTA on anti-leukemia immune response in AML, we initiated a study using clinical samples collected from AML patients. Here we report that VISTA is highly expressed on myeloid-derived suppressor cells (MDSCs) in the peripheral blood of AML patients. Both the frequency and intensity of VISTA expression on MDSCs are significantly higher in newly diagnosed AML than in healthy controls. Importantly knockdown of VISTA by specific siRNA potently reduced the MDSCs-mediated inhibition of CD8 T cell activity in AML, suggesting a suppressive effect of VISTA on anti-leukemia T cell response. Furthermore, we observed a strong positive association between MDSC expression of VISTA and T cell expression of PD-1 in AML. These results support the strategy of VISTA-targeted treatment for AML and underscore the strong potential for combined blockade of VISTA and PD-1 pathways in effective leukemia control.

show abstract

Section: Discussionmentioning

confidence: 99%

VISTA is highly expressed on MDSCs and mediates an inhibition of T cell response in patients with AML

et al. 2018

View full text Add to dashboard Cite

show abstract

“…The PD-1/PD-L1 pathway negatively regulates T-cell activation and functions, leading to the inhibition of immune responses in cancer patients. 9 Binding of PD-1 results in the formation of PD-1/TCR inhibitory microclusters that recruit SHP2 molecules, which dephosphorylate multiple members of the TCR signaling pathway, effectively turning off T-cell activation. 31 PD-1/PD-L1 blockage has been shown to be effective in patients with high PD-1 or PD-L1 expression and is used for the treatment of advanced melanoma.…”

Section: Ccl1mentioning

confidence: 99%

“…31 PD-1/PD-L1 blockage has been shown to be effective in patients with high PD-1 or PD-L1 expression and is used for the treatment of advanced melanoma. 9 Because HCC cells express high levels of PD-L1, like melanoma cells, 32 the blockage of the PD-1/PC-L1 pathway may also be effective against HCC. The study for efficacy assessment of PD-1 antibody has recently been designed in patients with advanced HCC.…”

Section: Ccl1mentioning

confidence: 99%

“…Binding of PD-1 to its ligand (PD-L1), expressed on tumor cells, results in the suppression of antitumor activities. 9 Anti-HCC immunotherapy utilizing CTL based on the blocking of the interaction between PD-1 and PD-L1 has been clinically tested. 10,11 Similarly, exhausted Mf express high levels of PD-1 upon recognition of a target antigen via the Toll-like receptor (TLR).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Host antitumor resistance improved by the macrophage polarization in a chimera model of patients with HCC

et al. 2017

View full text Add to dashboard Cite

show abstract

“…The development of immune checkpoint inhibitors has transformed the treatment of melanoma (1). Immune checkpoint inhibitors were the first class of therapy shown to improve the overall survival for patients with advanced melanoma.…”

Section: Introductionmentioning

confidence: 99%

Immune Checkpoint Inhibitors in the Treatment of Melanoma: From Basic Science to Clinical Application

Rausch¹,

Hastings

2017

Cutaneous Melanoma: Etiology and Therapy

View full text Add to dashboard Cite

Abstract:Immune checkpoint blockade has revolutionized the treatment of patients with advanced melanoma and many other cancers. Blockade of inhibitory receptors, CTLA-4 and PD-1, enhances T-cell-mediated antitumor immune responses, leading to improved survival and durable responses in patients. Based on their mechanism of action, immune checkpoint inhibitors can also induce immune-related adverse events that require careful monitoring and prompt treatment. Despite these successes, only a fraction of patients benefit from immune checkpoint blockade. Basic science approaches and clinical experience are defining predictive biomarkers to identify patients most likely to respond to therapy as well as mechanisms of resistance that limit responses in certain tumors or shorten the duration of response. New approaches and combination therapies are under development to broaden the clinical impact of immune checkpoint blockade by overcoming resistance to therapy and limiting adverse events.

show abstract

Targeting T Cell Co-receptors for Cancer Therapy

Cited by 425 publications

References 72 publications

VISTA is highly expressed on MDSCs and mediates an inhibition of T cell response in patients with AML

VISTA is highly expressed on MDSCs and mediates an inhibition of T cell response in patients with AML

Host antitumor resistance improved by the macrophage polarization in a chimera model of patients with HCC

Immune Checkpoint Inhibitors in the Treatment of Melanoma: From Basic Science to Clinical Application

Contact Info

Product

Resources

About