We are analyzing https://link.springer.com/article/10.1186/s13046-019-1085-3.

Title:
Challenges and potential of PD-1/PD-L1 checkpoint blockade immunotherapy for glioblastoma | Journal of Experimental & Clinical Cancer Research
Description:
PD-1/PD-L1 checkpoint blockades have achieved significant progress in several kinds of tumours. Pembrolizumab, which targets PD-1, has been approved as a first-line treatment for advanced non-small cell lung cancer (NSCLC) patients with positive PD-L1 expression. However, PD-1/PD-L1 checkpoint blockades have not achieved breakthroughs in treating glioblastoma because glioblastoma has a low immunogenic response and an immunosuppressive microenvironment caused by the precise crosstalk between cytokines and immune cells. A phase III clinical trial, Checkmate 143, reported that nivolumab, which targets PD-1, did not demonstrate survival benefits compared with bavacizumab in recurrent glioblastoma patients. Thus, the combination of a PD-1/PD-L1 checkpoint blockade with RT, TMZ, antibodies targeting other inhibitory or stimulatory molecules, targeted therapy, and vaccines may be an appealing solution aimed at achieving optimal clinical benefit. There are many ongoing clinical trials exploring the efficacy of various approaches based on PD-1/PD-L1 checkpoint blockades in primary or recurrent glioblastoma patients. Many challenges need to be overcome, including the identification of discrepancies between different genomic subtypes in their response to PD-1/PD-L1 checkpoint blockades, the selection of PD-1/PD-L1 checkpoint blockades for primary versus recurrent glioblastoma, and the identification of the optimal combination and sequence of combination therapy. In this review, we describe the immunosuppressive molecular characteristics of the tumour microenvironment (TME), candidate biomarkers of PD-1/PD-L1 checkpoint blockades, ongoing clinical trials and challenges of PD-1/PD-L1 checkpoint blockades in glioblastoma.
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Keywords {🔍}

pubmed, glioblastoma, article, google, scholar, cells, cas, checkpoint, cancer, cell, patients, central, pdpdl, blockades, combination, blockade, clinical, nivolumab, tumour, immune, efficacy, immunotherapy, expression, pdl, therapy, phase, res, immunosuppressive, clin, recurrent, antibody, tumours, treatment, response, ctla, checkmate, demonstrated, wang, ido, survival, found, study, factor, addition, immunol, microenvironment, tme, tim, tregs, primary,

Topics {✒️}

nivolumab 1 mg/kg + ipilimumab 3 mg/kg nivolumab 3 mg/kg + ipilimumab 1 mg/kg glucocorticoid-induced tnfr-related protein pd-1/pd-l1 signalling pathway granulocyte-macrophage colony-stumulating factor pd-1/pd-l1 checkpoint blockades inkt-cell-dependent airway hyperreactivity pd-1/pd-l1 checkpoint blockade receive nivolumab 3 mg/kg pd-1/pd-l1 pathway plays tumour-specific protein-encoding mutations b7-h1/pd-1 blockade therapy antibodies targeting pd-1/pd-l1 article download pdf pd-l1 checkpoint blockades positive pd-l1 expression pd-1/pd-l1 pathway [62] pd-1/pd-l1 pathway pd-1/pd-l1 blockade pd-1/ pd-l1 blockade pd-1/pd-ls pathway immune-related risk signature myeloid-derived suppressor cell van den boorn-konijnenberg cd4+cd25+ immunoreg- ulatory pd-1/pd-l1 interactions exonuclease proof-reading domain inhibit ifn-γ production measured pd-l1 expression pd-1/pd-l1 mechanism central nervous system drug toxicity-induced deaths idh-mutant type based pd-1+/tim3+ phenotype represents synthesized microenvironment-responsive nanoparticles post-trauma neuro-repair small-cell lung cancer observed pd-l1 expression tumour-inhibiting m1-tams cd4+cd25+ immunoregulatory cells restore anti-tumor immunity tumour infiltrating lymphocytes ox40/ox40l pathway enhanced inducing t-cell apoptosis tumour-cell-extrinsic factors [34] tumour mutational load anti-ox40 antibody offset tumor-infiltrating lymphocytes pd-1+/tim-3+ phenotype represents t-cell-poor microenvironment

Schema {🗺️}

WebPage:
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         headline:Challenges and potential of PD-1/PD-L1 checkpoint blockade immunotherapy for glioblastoma
         description:PD-1/PD-L1 checkpoint blockades have achieved significant progress in several kinds of tumours. Pembrolizumab, which targets PD-1, has been approved as a first-line treatment for advanced non-small cell lung cancer (NSCLC) patients with positive PD-L1 expression. However, PD-1/PD-L1 checkpoint blockades have not achieved breakthroughs in treating glioblastoma because glioblastoma has a low immunogenic response and an immunosuppressive microenvironment caused by the precise crosstalk between cytokines and immune cells. A phase III clinical trial, Checkmate 143, reported that nivolumab, which targets PD-1, did not demonstrate survival benefits compared with bavacizumab in recurrent glioblastoma patients. Thus, the combination of a PD-1/PD-L1 checkpoint blockade with RT, TMZ, antibodies targeting other inhibitory or stimulatory molecules, targeted therapy, and vaccines may be an appealing solution aimed at achieving optimal clinical benefit. There are many ongoing clinical trials exploring the efficacy of various approaches based on PD-1/PD-L1 checkpoint blockades in primary or recurrent glioblastoma patients. Many challenges need to be overcome, including the identification of discrepancies between different genomic subtypes in their response to PD-1/PD-L1 checkpoint blockades, the selection of PD-1/PD-L1 checkpoint blockades for primary versus recurrent glioblastoma, and the identification of the optimal combination and sequence of combination therapy. In this review, we describe the immunosuppressive molecular characteristics of the tumour microenvironment (TME), candidate biomarkers of PD-1/PD-L1 checkpoint blockades, ongoing clinical trials and challenges of PD-1/PD-L1 checkpoint blockades in glioblastoma.
         datePublished:2019-02-18T00:00:00Z
         dateModified:2019-02-18T00:00:00Z
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            Nivolumab
            Tumour infiltrating lymphocytes
            Tumour mutation load
            Temozolomide
            Cancer Research
            Immunology
            Apoptosis
            Oncology
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ScholarlyArticle:
      headline:Challenges and potential of PD-1/PD-L1 checkpoint blockade immunotherapy for glioblastoma
      description:PD-1/PD-L1 checkpoint blockades have achieved significant progress in several kinds of tumours. Pembrolizumab, which targets PD-1, has been approved as a first-line treatment for advanced non-small cell lung cancer (NSCLC) patients with positive PD-L1 expression. However, PD-1/PD-L1 checkpoint blockades have not achieved breakthroughs in treating glioblastoma because glioblastoma has a low immunogenic response and an immunosuppressive microenvironment caused by the precise crosstalk between cytokines and immune cells. A phase III clinical trial, Checkmate 143, reported that nivolumab, which targets PD-1, did not demonstrate survival benefits compared with bavacizumab in recurrent glioblastoma patients. Thus, the combination of a PD-1/PD-L1 checkpoint blockade with RT, TMZ, antibodies targeting other inhibitory or stimulatory molecules, targeted therapy, and vaccines may be an appealing solution aimed at achieving optimal clinical benefit. There are many ongoing clinical trials exploring the efficacy of various approaches based on PD-1/PD-L1 checkpoint blockades in primary or recurrent glioblastoma patients. Many challenges need to be overcome, including the identification of discrepancies between different genomic subtypes in their response to PD-1/PD-L1 checkpoint blockades, the selection of PD-1/PD-L1 checkpoint blockades for primary versus recurrent glioblastoma, and the identification of the optimal combination and sequence of combination therapy. In this review, we describe the immunosuppressive molecular characteristics of the tumour microenvironment (TME), candidate biomarkers of PD-1/PD-L1 checkpoint blockades, ongoing clinical trials and challenges of PD-1/PD-L1 checkpoint blockades in glioblastoma.
      datePublished:2019-02-18T00:00:00Z
      dateModified:2019-02-18T00:00:00Z
      pageStart:1
      pageEnd:13
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      sameAs:https://doi.org/10.1186/s13046-019-1085-3
      keywords:
         Glioblastoma multiforme
         Nivolumab
         Tumour infiltrating lymphocytes
         Tumour mutation load
         Temozolomide
         Cancer Research
         Immunology
         Apoptosis
         Oncology
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                     type:PostalAddress
                  type:Organization
                  name:Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences
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                     type:PostalAddress
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                  name:Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences
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                  address:
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         name:Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, China
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      address:
         name:Key Laboratory of Post-Trauma Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin, China
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      address:
         name:Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, China
         type:PostalAddress
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         type:PostalAddress
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               name:Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, China
               type:PostalAddress
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            name:Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences
            address:
               name:Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, China
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               name:Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China
               type:PostalAddress
            type:Organization
            name:Key Laboratory of Post-Trauma Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education
            address:
               name:Key Laboratory of Post-Trauma Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin, China
               type:PostalAddress
            type:Organization
            name:Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System
            address:
               name:Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, China
               type:PostalAddress
            type:Organization
      name:Hui Guan
      affiliation:
            name:The Fourth People’s Hospital of Jinan
            address:
               name:Department of Radiation Oncology, The Fourth People’s Hospital of Jinan, Jinan, China
               type:PostalAddress
            type:Organization
      name:Yang Yu
      affiliation:
            name:Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences
            address:
               name:Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, China
               type:PostalAddress
            type:Organization
      name:Jie Lu
      affiliation:
            name:Shandong Province Qianfoshan Hospital of Shandong University
            address:
               name:Department of Neurosurgery, Shandong Province Qianfoshan Hospital of Shandong University, Jinan, China
               type:PostalAddress
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      email:[email protected]
      name:Jinming Yu
      affiliation:
            name:Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences
            address:
               name:Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, China
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, China
      name:Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, China
      name:Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China
      name:Key Laboratory of Post-Trauma Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin, China
      name:Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, China
      name:Department of Radiation Oncology, The Fourth People’s Hospital of Jinan, Jinan, China
      name:Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, China
      name:Department of Neurosurgery, Shandong Province Qianfoshan Hospital of Shandong University, Jinan, China
      name:Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, China

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