Immune checkpoint ≈ Immune checkpoint
View article: PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer
PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer Open
Immune checkpoint inhibition represents a major recent breakthrough in the treatment of malignant diseases including breast cancer. Blocking the programmed death receptor-1 (PD-1) and its ligand, PD-L1, has shown impressive antitumor activ…
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Cancer immunotherapy using checkpoint blockade Open
The release of negative regulators of immune activation (immune checkpoints) that limit antitumor responses has resulted in unprecedented rates of long-lasting tumor responses in patients with a variety of cancers. This can be achieved by …
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Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq Open
Single-cell expression profiles of melanoma Tumors harbor multiple cell types that are thought to play a role in the development of resistance to drug treatments. Tirosh et al. used single-cell sequencing to investigate the distribution of…
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IFN-γ–related mRNA profile predicts clinical response to PD-1 blockade Open
Programmed death-1-directed (PD-1-directed) immune checkpoint blockade results in durable antitumor activity in many advanced malignancies. Recent studies suggest that IFN-γ is a critical driver of programmed death ligand-1 (PD-L1) express…
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Mutations Associated with Acquired Resistance to PD-1 Blockade in Melanoma Open
In this study, acquired resistance to PD-1 blockade immunotherapy in patients with melanoma was associated with defects in the pathways involved in interferon-receptor signaling and in antigen presentation. (Funded by the National Institut…
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Fulminant Myocarditis with Combination Immune Checkpoint Blockade Open
Immune checkpoint inhibitors have improved clinical outcomes associated with numerous cancers, but high-grade, immune-related adverse events can occur, particularly with combination immunotherapy. We report the cases of two patients with m…
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PD-1 expression by tumour-associated macrophages inhibits phagocytosis and tumour immunity Open
Programmed cell death protein 1 (PD-1) is an immune checkpoint receptor that is upregulated on activated T cells for the induction of immune tolerance. Tumour cells frequently overexpress the ligand for PD-1, programmed cell death ligand 1…
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Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance Open
Immune checkpoint inhibitors (ICIs) have made an indelible mark in the field of cancer immunotherapy. Starting with the approval of anti-cytotoxic T lymphocyte-associated protein 4 (anti-CTLA-4) for advanced-stage melanoma in 2011, ICIs—wh…
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B cells are associated with survival and immunotherapy response in sarcoma Open
Soft-tissue sarcomas represent a heterogeneous group of cancer, with more than 50 histological subtypes1,2. The clinical presentation of patients with different subtypes is often atypical, and responses to therapies such as immune checkpoi…
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PD-1 and PD-L1 Checkpoint Signaling Inhibition for Cancer Immunotherapy: Mechanism, Combinations, and Clinical Outcome Open
Several cancers are highly refractory to conventional chemotherapy. The survival of tumors in several cases is assisted by checkpoint immunomodulation to maintain the imbalance between immune surveillance and cancer cell proliferation. Che…
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Tumor aneuploidy correlates with markers of immune evasion and with reduced response to immunotherapy Open
Chromosomal chaos and tumor immunity Cancer immunotherapy produces durable clinical responses in only a subset of patients. Identification of tumor characteristics that correlate with responses could lead to predictive biomarkers and shed …
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Tumor-associated macrophages in tumor metastasis: biological roles and clinical therapeutic applications Open
Tumor metastasis is a major contributor to the death of cancer patients. It is driven not only by the intrinsic alterations in tumor cells, but also by the implicated cross-talk between cancer cells and their altered microenvironment compo…
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MYC regulates the antitumor immune response through CD47 and PD-L1 Open
Oncogene control of antitumor immunity Recent clinical success of cancer immunotherapy has intensified interest in how tumors normally evade the immune response. Whether and how oncogenes contribute to this process are not well understood.…
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Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations Open
Melanoma, a skin cancer associated with high mortality rates, is highly radio- and chemotherapy resistant but can also be very immunogenic. These circumstances have led to a recent surge in research into therapies aiming to boost anti-tumo…
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Immune checkpoint signaling and cancer immunotherapy Open
Immune checkpoint blockade therapy has become a major weapon in fighting cancer. Antibody drugs, such as anti-PD-1 and anti-PD-L1, demonstrate obvious advantages such as broad applicability across cancer types and durable clinical response…
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Genomic correlates of response to immune checkpoint therapies in clear cell renal cell carcinoma Open
SNF'ing out antitumor immunity Immune checkpoint inhibitors induce durable tumor regressions in some, but not all, cancer patients. Understanding the mechanisms that determine tumor sensitivity to these drugs could potentially expand the n…
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Suppression of Exosomal PD-L1 Induces Systemic Anti-tumor Immunity and Memory Open
PD-L1 on the surface of tumor cells binds its receptor PD-1 on effector T cells, thereby suppressing their activity. Antibody blockade of PD-L1 can activate an anti-tumor immune response leading to durable remissions in a subset of cancer …
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Cancer immunotherapy: the beginning of the end of cancer? Open
These are exciting times for cancer immunotherapy. After many years of disappointing results, the tide has finally changed and immunotherapy has become a clinically validated treatment for many cancers. Immunotherapeutic strategies include…
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Genomic Features of Response to Combination Immunotherapy in Patients with Advanced Non-Small-Cell Lung Cancer Open
Combination immune checkpoint blockade has demonstrated promising benefit in lung cancer, but predictors of response to combination therapy are unknown. Using whole-exome sequencing to examine non-small-cell lung cancer (NSCLC) treated wit…
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Review of Indications of FDA-Approved Immune Checkpoint Inhibitors per NCCN Guidelines with the Level of Evidence Open
Cancer is associated with higher morbidity and mortality and is the second leading cause of death in the US. Further, in some nations, cancer has overtaken heart disease as the leading cause of mortality. Identification of molecular mechan…
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CTLA-4: a moving target in immunotherapy Open
CD28 and CTLA-4 are members of a family of immunoglobulin-related receptors that are responsible for various aspects of T-cell immune regulation. The family includes CD28, CTLA-4, and ICOS as well as other proteins, including PD-1, BTLA, a…
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Immune Checkpoint Inhibitors in Cancer Therapy Open
The discovery of immune checkpoint proteins such as PD-1/PDL-1 and CTLA-4 represents a significant breakthrough in the field of cancer immunotherapy. Therefore, humanized monoclonal antibodies, targeting these immune checkpoint proteins ha…
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Large-scale public data reuse to model immunotherapy response and resistance Open
Despite growing numbers of immune checkpoint blockade (ICB) trials with available omics data, it remains challenging to evaluate the robustness of ICB response and immune evasion mechanisms comprehensively. To address these challenges, we …
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Immune-related adverse events and anti-tumor efficacy of immune checkpoint inhibitors Open
Although immune checkpoint inhibitors (ICIs) have transformed the treatment landscape for patients with many advanced malignancies, only 15-60% of patients respond, leaving a broad swath of patients who do not derive benefit. Identifying b…
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Human CAR T cells with cell-intrinsic PD-1 checkpoint blockade resist tumor-mediated inhibition Open
Following immune attack, solid tumors upregulate coinhibitory ligands that bind to inhibitory receptors on T cells. This adaptive resistance compromises the efficacy of chimeric antigen receptor (CAR) T cell therapies, which redirect T cel…
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Nivolumab in Patients With Relapsed or Refractory Hematologic Malignancy: Preliminary Results of a Phase Ib Study Open
Purpose Cancer cells can exploit the programmed death-1 (PD-1) immune checkpoint pathway to avoid immune surveillance by modulating T-lymphocyte activity. In part, this may occur through overexpression of PD-1 and PD-1 pathway ligands (PD-…
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Analysis of Immune Signatures in Longitudinal Tumor Samples Yields Insight into Biomarkers of Response and Mechanisms of Resistance to Immune Checkpoint Blockade Open
Immune checkpoint blockade represents a major breakthrough in cancer therapy; however, responses are not universal. Genomic and immune features in pretreatment tumor biopsies have been reported to correlate with response in patients with m…
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The role of PD-L1 expression as a predictive biomarker: an analysis of all US Food and Drug Administration (FDA) approvals of immune checkpoint inhibitors Open
The development of immune checkpoint inhibitors has changed the treatment paradigm for advanced cancers across many tumor types. Despite encouraging and sometimes durable responses in a subset of patients, most patients do not respond. Tum…
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Neoadjuvant checkpoint blockade for cancer immunotherapy Open
Presurgical immune checkpoint blockade Checkpoint blockade immunotherapy using antibodies that inhibit the programmed cell death 1 (PD-1) or cytotoxic T lymphocyte–associated protein 4 (CTLA-4) pathways has resulted in unprecedented clinic…
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Integrated molecular analysis of tumor biopsies on sequential CTLA-4 and PD-1 blockade reveals markers of response and resistance Open
Profiling of melanoma patients treated with checkpoint blockade reveals TCR clonality and copy number loss as correlates of therapeutic response.