Cutting Edge: CD28 Engagement Releases Antigen-Activated Invariant NKT Cells from the Inhibitory Effects of PD-1

Wang, Jianxiong; Lu, Cheng; Wondimu, Zenebech; Swain, Mark G.; Santamaría, Pere; Yang, Yang

doi:10.4049/jimmunol.0804050

Cited by 32 publications

(33 citation statements)

References 21 publications

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“…Second, patients with high PD-1 þ -CD8 expression should be carefully monitored after treatments and considered for advanced therapies. 2 The inhibitory effects of PD-1 and B7-H1 can be overcome by certain immunoactivators, 36,37 and blocking PD-1 and B7-H1 restores the anti-tumor activity of TILs in some cancers, 14,15,22 which indicates that local immunosuppression in tumors can be reversed. Therefore, we hypothesize that alleviating the strong local immunosuppression of nasopharyngeal carcinoma by counteracting PD-1 and its ligands will not only improve the outcomes of Epstein-Barr virustargeted cancer immunotherapy, but also improve the efficacy of conventional nasopharyngeal carcinoma therapy.…”

Section: Discussionmentioning

confidence: 99%

Increase of programmed death-1-expressing intratumoral CD8 T cells predicts a poor prognosis for nasopharyngeal carcinoma

et al. 2010

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Intratumoral cytotoxic T lymphocytes are critical for controlling tumor recurrence, and programmed death-1 (PD-1) is a recognized marker of T-cell dysfunction. We analyzed this marker and its binding ligands in nasopharyngeal tumor tissue and non-cancerous nasopharyngeal control tissue to retrospectively evaluate the correlation between its expression and the post-treatment outcome of nasopharyngeal carcinoma patients. Using double immunofluorescence staining, we found that the expression of PD-1 in CD8 T cells in tumor tissue was significantly higher than in control tissue (mean: 28.4 vs 3.9%, Po0.0001). Although the expression rate of PD-1 in intratumoral CD8 cells was not associated with the other clinicopathological parameters examined, the higher expression rate in this subset of T cells significantly correlated with a poorer prognosis of overall survival, disease-free survival, and locoregional recurrence-free survival of the cancer patients (P ¼ 0.05, 0.007, and 0.004, respectively). Multivariate analysis confirmed it as an independent risk factor for death, treatment failure, and local recurrence of nasopharyngeal carcinoma. On the other hand, the expression of PD-1 in CD4 T cells and of its ligands in epithelial and stromal cells was not significantly different between tumor and control tissue, and its expression was not associated with clinical outcome of the cancer patients. We propose that PD-1 expression in CD8 cells reflects the selective suppression of cytotoxic lymphocytes in the tumor microenvironment and predicts recurrence of nasopharyngeal carcinoma after conventional therapies.

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Section: Discussionmentioning

confidence: 99%

Increase of programmed death-1-expressing intratumoral CD8 T cells predicts a poor prognosis for nasopharyngeal carcinoma

et al. 2010

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“…More recently, it has been demonstrated that PD-1, another inhibitory coreceptor, is expressed on NKT cells (28) and that the engagement of PD-1 on NKT cells by PD-1 ligand 1 inhibits cytokine secretion by a-GalCer-activated NKT cells (33). CD94/ NKG2A, an inhibitory receptor on NK cells, is also expressed on NKT cells, and the blockade of NKG2A-mediated inhibitory signal with an antagonistic Ab augments Con A-and a-GalCerinduced liver injury (34).…”

Section: Discussionmentioning

confidence: 99%

Protective Roles of B and T Lymphocyte Attenuator in NKT Cell-Mediated Experimental Hepatitis

Iwata¹,

Watanabe²,

Oya³

et al. 2009

The Journal of Immunology

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Although B and T lymphocyte attenuator (BTLA) was originally identified as an inhibitory coreceptor selectively expressed on Th1 cells and B cells, recent studies have revealed that BTLA is expressed on a variety of cells, including macrophages, dendritic cells, and NK cells, and modulates their functions. However, the role of BTLA in the regulation of NKT cell function remains unknown. In this study, we found that BTLA was expressed on NKT cells at the levels similar to those on T cells and that BTLA-deficient (BTLA−/−) NKT cells produced larger amounts of IL-4 and IFN-γ upon α-glactosylceramide stimulation as compared with wild-type (WT) NKT cells. In vivo, BTLA−/− mice produced larger amounts of IL-4 and IFN-γ upon Con A injection and were more susceptible to Con A-induced hepatitis than WT mice. In addition, the augmentation of Con A-induced hepatitis in BTLA−/− mice was not observed in BTLA/NKT-double deficient mice. Moreover, NKT−/− mice reconstituted with BTLA−/− NKT cells were significantly more susceptible to Con A-induced hepatitis as compared with NKT −/− mice reconstituted with WT NKT cells. These results suggest that BTLA functions as the inhibitory coreceptor of NKT cells and plays a critical role in the prevention of NKT cell-mediated liver injury.

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“…Activated NKT (26), B cells (27), and DC (28) can also express PD-1 and be suppressed through the PD-1 pathway. Early studies demonstrated that PD-L1 + murine and human tumor cells induce apoptosis of activated T cells and that antibody blocking of PD-L1 facilitates anti-tumor immunity (13, 14).…”

Section: Pd-l1 and Pd-1 Mediate Immune Suppression By Multiple Mechanmentioning

confidence: 99%

The Programmed Death-1 Immune-Suppressive Pathway: Barrier to Antitumor Immunity

Ostrand‐Rosenberg

Horn

Haile

2014

The Journal of Immunology

190

151

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Programmed Death Ligand 1 (PD-L1, also known as B7 homolog 1 (B7-H1) or CD274) is a major obstacle to anti-tumor immunity because it (i) tolerizes/anergizes tumor-reactive T cells by binding to its receptor PD-1 (CD279); (ii) renders tumor cells resistant to CD8+ T cell and FasL-mediated lysis; and (iii) tolerizes T cells by reverse signalling through T cell-expressed CD80. PD-L1 is abundantly present in the tumor microenvironment where it is expressed by many malignant cells as well as by immune cells and vascular endothelial cells. The critical role of PD-L1 in obstructing anti-tumor immunity has been demonstrated in multiple animal models and in recent clinical trials. This article reviews the mechanisms by which PD-L1 impairs anti-tumor immunity and discusses established and experimental strategies for maintaining T cell activation in the presence of PD-L1-expressing cells in the tumor microenvironment.

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Cutting Edge: CD28 Engagement Releases Antigen-Activated Invariant NKT Cells from the Inhibitory Effects of PD-1

Cited by 32 publications

References 21 publications

Increase of programmed death-1-expressing intratumoral CD8 T cells predicts a poor prognosis for nasopharyngeal carcinoma

Increase of programmed death-1-expressing intratumoral CD8 T cells predicts a poor prognosis for nasopharyngeal carcinoma

Protective Roles of B and T Lymphocyte Attenuator in NKT Cell-Mediated Experimental Hepatitis

The Programmed Death-1 Immune-Suppressive Pathway: Barrier to Antitumor Immunity

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