B7-H1 on myeloid-derived suppressor cells in immune suppression by a mouse model of ovarian cancer

Liu, Yu; Zeng, Bin; Zhang, Zhuohan; Yuan, Zihao; Yang, Rongcun

doi:10.1016/j.clim.2008.07.030

Cited by 93 publications

(70 citation statements)

References 49 publications

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“…Although it was anticipated that this population would comprise immunosuppressive MDSCs, our results were not consistent with previous studies (20)(21)(22). This population did not represent vascular leukocyte cells based on either phenotypic or functional differences (23)(24)(25).…”

contrasting

confidence: 99%

“…We initially assumed that the CD11b + Gr-1 + cells accumulating in the spleen (ID8/spleen) and ascites (ID8/ascites) of the ID8-bearing mice would consist of MDSCs as previously described (20,21,29). Surprisingly, CD11b + Gr-1 + cells from both compartments did not suppress but rather enhanced both CD4 + and CD8 + T cell proliferation in vitro in both a nonspecific and an Ag-FIGURE 1.…”

Section: Cd11b + Gr-1 + Cells From Malignant Ascites Are Not Mdscsmentioning

confidence: 92%

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Antigen-Specific Immunity and Cross-Priming by Epithelial Ovarian Carcinoma-Induced CD11b+Gr-1+ Cells

Tomihara

Guo

Shin

et al. 2010

The Journal of Immunology

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Both innate and adaptive immune systems are considered important for cancer prevention, immunosurveillance, and control of cancer progression. It is known that, although both systems initially eliminate emerging tumor cells efficiently, tumors eventually escape immune attack by a variety of mechanisms, including differentiation and recruitment of immunosuppressive CD11b+Gr-1+ myeloid suppressor cells into the tumor microenvironment. However, we show that CD11b+Gr-1+ cells found in ascites of epithelial ovarian cancer-bearing mice at advanced stages of disease are immunostimulatory rather than being immunosuppressive. These cells consist of a homogenous population of cells that morphologically resemble neutrophils. Moreover, like dendritic cells, immunostimulatory CD11b+Gr-1+ cells can strongly cross-prime, augmenting the proliferation of functional CTLs via signaling through the expression of costimulatory molecule CD80. Adoptive transfer of these immunostimulatory CD11b+Gr-1+ cells from ascites of ovarian cancer-bearing mice results in the significant regression of s.c. tumors even without being pulsed with exogenous tumor Ag prior to adoptive transfer. We now show for the first time that adaptive immune responses against cancer can be augmented by these cancer-induced granulocyte-like immunostimulatory myeloid (CD11b+Gr-1+) cells, thereby mediating highly effective antitumor immunity in an adoptive transfer model of immunity.

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contrasting

confidence: 99%

Section: Cd11b + Gr-1 + Cells From Malignant Ascites Are Not Mdscsmentioning

confidence: 92%

Antigen-Specific Immunity and Cross-Priming by Epithelial Ovarian Carcinoma-Induced CD11b+Gr-1+ Cells

Tomihara

Guo

Shin

et al. 2010

The Journal of Immunology

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“…This success has encouraged greater exploration of how multiple immune pathways can be harnessed for therapeutic benefit. PD-L1 has been identified as a key regulator of the immune response, with potential utility for the treatment of cancer, a role supported by a range of preclinical studies in mice (15,(20)(21)(22)(23)25). More recently, the blockade of PD-L1 signaling has received even greater attention due to encouraging data from clinical trials assessing the activity of anti-PD-L1 and anti-PD-1 antibodies in late stage cancer patients, and the successful registration of the anti-PD-1 antibodies nivolumab and pembrolizumab for the treatment of melanoma and nonsmall cell lung cancer (NSCLC; refs.…”

Section: Discussionmentioning

confidence: 99%

“…Based in part on these observations, anti-PD-L1 antibodies could be used therapeutically to enhance antitumor immune responses in patients with cancer. In fact, multiple preclinical studies have demonstrated antitumor activity for anti-PD-L1 or anti-PD-1 antibodies in mouse models (15,(20)(21)(22)(23)(24)(25), and two recently completed phase I clinical trials have similarly reported encouraging activity signals for anti-PD-L1 (26,27) and anti-PD-1 (28)(29)(30)(31) in patients.…”

Section: Introductionmentioning

confidence: 99%

Identification and Characterization of MEDI4736, an Antagonistic Anti–PD-L1 Monoclonal Antibody

Stewart¹,

Morrow²,

Hammond³

et al. 2015

Cancer Immunology Research

347

255

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Programmed cell-death 1 ligand 1 (PD-L1) is a member of the B7/CD28 family of proteins that control T-cell activation. Many tumors can upregulate expression of PD-L1, inhibiting antitumor T-cell responses and avoiding immune surveillance and elimination. We have identified and characterized MEDI4736, a human IgG1 monoclonal antibody that binds with high affinity and specificity to PD-L1 and is uniquely engineered to prevent antibody-dependent cell-mediated cytotoxicity. In vitro assays demonstrate that MEDI4736 is a potent antagonist of PD-L1 function, blocking interaction with PD-1 and CD80 to overcome inhibition of primary human T-cell activation. In vivo MEDI4736 significantly inhibits the growth of human tumors in a novel xenograft model containing coimplanted human T cells. This activity is entirely dependent on the presence of transplanted T cells, supporting the immunological mechanism of action for MEDI4736. To further determine the utility of PD-L1 blockade, an anti-mouse PD-L1 antibody was investigated in immunocompetent mice. Here, anti-mouse PD-L1 significantly improved survival of mice implanted with CT26 colorectal cancer cells. The antitumor activity of anti-PD-L1 was enhanced by combination with oxaliplatin, which resulted in increased release of HMGB1 within CT26 tumors. Taken together, our results demonstrate that inhibition of PD-L1 function can have potent antitumor activity when used as monotherapy or in combination in preclinical models, and suggest it may be a promising therapeutic approach for the treatment of cancer. MEDI4736 is currently in several clinical trials both alone and in combination with other agents, including anti-CTLA-4, anti-PD-1, and inhibitors of IDO, MEK, BRAF, and EGFR.

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“…Persistently high levels of PD-1 expression occur during chronic antigen exposure resulting in T cell exhaustion. Interestingly, the PD-1:PD-L1/L2 interaction upon T cell infiltrating lymphocytes (TILs), myeloid cells and tumor cells appears to be a major mechanism of immune evasion in cancer [124][125][126][127][128][129][130][131]. PD-L1 expression on GBM tumor cells increases with loss of phosphatase and tensin homolog (PTEN) and activation of the phosphatidylinositol-3-OH kinase (PI3K) pathway [89].…”

Section: Immune Checkpoint Therapymentioning

confidence: 99%

Immunotherapy for Glioblastoma

Theodros¹,

Moran²,

Garzón-Muvdi³

et al. 2016

J Clin Cell Immunol

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Glioblastoma (GBM) is the most common primary malignant brain cancer with a dismal prognosis in spite of aggressive treatment options. Although once thought to be an "immune-privileged" site, recent advances have begun to highlight the complex interaction between the immune system and the central nervous system. Thus, great interest has emerged in the ability of immunotherapy to potentially prolong the survival of patients suffering from GBM. Indeed, numerous clinical trials have demonstrated durable responses in late stage disease, as well as, among patients with brain metastasis. A variety of approaches to modulating the immune system exist and their efficacy are currently being investigated in various clinical trials. Here we provide a brief overview of neuroimmunology and explore the various approaches towards priming the immune system against GBM.

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B7-H1 on myeloid-derived suppressor cells in immune suppression by a mouse model of ovarian cancer

Cited by 93 publications

References 49 publications

Antigen-Specific Immunity and Cross-Priming by Epithelial Ovarian Carcinoma-Induced CD11b+Gr-1+ Cells

Antigen-Specific Immunity and Cross-Priming by Epithelial Ovarian Carcinoma-Induced CD11b+Gr-1+ Cells

Identification and Characterization of MEDI4736, an Antagonistic Anti–PD-L1 Monoclonal Antibody

Immunotherapy for Glioblastoma

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