check point blockade

BACKGROUND: Immune check-point blockade (ICB) has shown clinical benefit in mismatch repair-deficient/microsatellite instability high metastatic colorectal cancer (mCRC) but not in mismatch repair-proficient/microsatellite stable patients. Cancer vaccines with autologous dendritic cells (ADC) could be a complementary therapeutic approach to ICB as this combination has the potential to achieve synergistic effects. METHODS: This was a Phase I/II multicentric study with translational sub-studies, to evaluate the safety, pharmacodynamics and anti-tumor effects of Avelumab plus ADC vaccine in heavily pre-treated MSS mCRC patients...

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy characterized by high resistance and poor response to chemotherapy. In addition, the poorly immunogenic pancreatic tumors constitute an immunosuppressive tumor microenvironment (TME), that render immunotherapy-based approaches ineffective. Understanding the mechanisms of therapy resistance, identifying new targets, and developing effective strategies to overcome resistance can significantly impact the management of patients with PDAC. Chemokines are small soluble factors that are significantly deregulated during PDAC pathogenesis, contributing to tumor growth, metastasis, immune cell trafficking, and therapy resistance...

Aim: There is an unmet need for predictive biomarkers for immune checkpoint blockade in ovarian cancer. Homologous recombination deficiency (HRD) and immunoreactive molecular subtype may be associated with determinants of immunogenicity. Materials & methods: Neoantigen load, tumor inflammation signature (TIS), immune cell infiltrates and individual immune checkpoints were assessed based on HRD status and molecular subtype. Results: Tumors with HRD demonstrated significantly higher expression of neoantigens and multiple immune check points, but not higher TIS scores or increased immune cell infiltrates...

Background: Liver cancer is the most malignant type of human malignancies. In recent years, immune therapy that targets the immune check points such as programmed cell death ligand 1 (PD-L1) has achieve great success. Abrine is the dominant alkaloid in Abrus cantoniensis and Abrus precatorius Linn. that exhibited anticancer effect. This work is aimed at studying the effects of abrine in immunity of liver cancer. Methods: Cell viability, proliferation, and migration were assessed by CCK-8, Edu, and Transwell assay...

Effective cancer therapy aims to treat not only primary tumors but also metastatic and recurrent cancer. Immune check point blockade-mediated immunotherapy showed promising effect against tumors; however, it still has a limited effect in metastatic or recurrent cancer. Here, we extracted recombinant murine programmed death-1 (rmPD-1) proteins. The extracted rmPD-1 effectively bound to CT-26 and 4T1 cells expressing PD-L1 and PD-L2. The rmPD-1 did not alter the activation of dendritic cells (DCs); however, rmPD-1 promoted T cell-mediated anti-cancer immunity against CT-26 tumors in mice...

In 2007, an HIV-infected individual (Berlin patient) underwent two allogeneic haematopoietic stem cell transplantations (allo-HSCTs) from a donor with a homozygous mutation in the HIV co-receptor CCR5 (CCR5Δ32) for the treatment of acute myeloid leukaemia, which eradicated HIV from infected patients simultaneously. Ten years later, another success in the 'London patient' was reported. These two cases suggest that allo-HSCT from a suitable donor is feasible for the treatment of haematological malignancies and HIV...

Immunotherapy using PD-1 and CTLA4 inhibitors to stimulate T cell immunity has achieved significant clinical success. However, only a portion of patients benefit from T cell-based immunotherapy. Macrophages, the most abundant type of innate immune cells in the body, play an important role in eliminating tumor cells and infectious microbes. The phagocytic check point protein CD47 inhibits the phagocytic activity of macrophages through binding to SIRPα expressed on macrophages. Blockade of the interaction between CD47 and SIRPα could restore phagocytic activity and eliminate tumor cells in vitro and in vivo...

Malignant peritoneal mesothelioma is a rare malignancy arising from the serosa of the peritoneal cavity. It is diagnosed based on suspicious findings on cross sectional imaging and a tissue biopsy showing confirmatory histologic and immunohistochemical features. The disease is hallmarked by its propensity to progress mainly in the peritoneal cavity. In selected patients, surgical cytoreduction and hyperthermic intra-operative peritoneal chemotherapy has become the initial preferred treatment and is associated with provide prolonged in many patients...

This review is devoted to a rare in clinical practice, but promising phenomenon of regression distant non-irradiated metastases in combination therapy of cancer patients. R. H. Mole in 1953 suggested introducing the term "abscopal effect" to denote the effect of ionizing radiation "at a distance from the irradiated volume but within the same organism." Currently, it is a hypothesis in the treatment of metastatic cancer, when there is a regression of untreated areas simultaneously with a decrease in the tumor...

PURPOSE: To assess response to programmed death-1 (PD-1) monotherapy (nivolumab) in hepatocellular carcinoma (HCC) patients using RECIST1.1, modified RECIST (mRECIST), and immune RECIST (iRECIST). A secondary objective was to identify clinicolaboratory and imaging variables predictive of progressive disease (PD) and overall survival (OS). METHODS: Patients with HCC treated with nivolumab at a single institution from 5/2016 to 12/2019 with MRI or CT performed ≥ 4 weeks post treatment were retrospectively assessed...

Pericapsular Nerve Group (PENG) is a new regional method for the hip surgery. It can be easily performed under ultrasound control and can provide adequate anesthesia without muscle weakness. The aim of the study was to estimate the clinical effectiveness of the Pericapsular Nerve Group block after hip arthroplasty in terms of analgesia and physical activity of patients. The study included 30 patients (male/female=14/16) with ASA II-III physical status, the average age of the patients was 63.1±12.5 years, who undergone elective primary total hip arthroplasty for coxarthrosis or hip fracture under spinal anesthesia...

Immune checkpoint inhibitors (ICIs), including programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 have shown promising cancer clinical outcomes. However, IC therapy has low patient response rates (10%-15%). Thus, ICIs and sufficient antigen combinations into the tumor microenvironment (TME) is important to produce strong tumor-specific adaptive immune responses. Mice were treated with cisplatin, and human cancer cells were exposed to inflammatory cytokines, to confirm increased PD-L1 and major histocompatibility complex (MHC) I expression by tumor cells or dendritic cells...

Immune checkpoint blockade (ICB) antibodies targeting programmed cell death ligand-1 (PD-L1) and programmed cell death-1 (PD-1) have improved survival in patients with conventional single agent chemotherapy-resistant gestational trophoblastic neoplasia (GTN). However, many patients are resistant to ICB therapy, the mechanisms of which are poorly understood. Unraveling the regulatory mechanism for PD-L1 expression may provide a new strategy to improve ICB therapy in patients with GTN. Here, we investigated whether the ezrin/radixin/moesin (ERM) family, i...

Cancer cells employ programmed cell death ligand-1 (PD-L1), an immune checkpoint protein that binds to programmed cell death-1 (PD-1) and is highly expressed in various cancers, including cervical carcinoma, to abolish T-cell-mediated immunosurveillance. Despite a key role of PD-L1 in various cancer cell types, the regulatory mechanism for PD-L1 expression is largely unknown. Understanding this mechanism could provide a novel strategy for cervical cancer therapy. Here, we investigated the influence of ezrin/radixin/moesin (ERM) family scaffold proteins, crosslinking the actin cytoskeleton and certain plasma membrane proteins, on the expression of PD-L1 in HeLa cells...

OBJECTIVES: Programmed death-1(PD-1)/programmed death ligand-1 (PD-L1) antibodies have clinical benefits for cancer patients facing immune-related adverse events (irAEs). However, the effect of steroid use on the prognosis of patients with non-small cell lung cancer (NSCLC) receiving PD-1 blockade remains unclear. METHODS: NSCLC patients with complete response (CR)/partial response (PR) or stable disease (SD)/not evaluable (NE) status plus progression-free survival (PFS) of 180 days after PD-1 blockade from December 2015 to December 2018 were retrospectively registered in our study and were divided into two groups: those with and without systemic steroid use for irAEs...

BACKGROUND: Epstein-Barr virus (EBV) is detected in a variety of B-cell lymphomas (BCLs) and B-cell lymphoproliferative disorders (B-LPDs). Immunodeficiency has been considered to play a key role in the pathogenesis of these diseases. In addition, immune escape of tumor cells may also contribute to the development of EBV+ BCLs and B-LPDs. The PD-1/PD-L1 pathway is particularly important for immune escape of tumor cells that contribute to development of lymphoma through suppression of cytotoxic T-cell function...

Context: Thyrotoxicosis is a common immune-related adverse event in patients treated with programmed cell death protein-1 (PD1) or programmed cell death protein ligand-1 (PD-L1) blockade. A detailed endocrinological assessment, including thyroid ultrasound and scintigraphy, is lacking, as are data on response to treatment and follow-up. Objective: The aim of this study was to better characterize the thyrotoxicosis secondary to immune checkpoint inhibitors, gaining insights into pathogenesis and treatment...

The immune system removes abnormal and cancerous cells by way of T-cell detection at immune checkpoints. Cancerous cells, due to their expression of proteins such as T-cell inactivating programmed death-ligand 1 (PD-L1), may evade the immune system resulting in replication and ultimately metastases. Immunotherapy in the form of checkpoint blockade, such as anti-programmed cell death 1 (PD-1) monoclonal antibody pembrolizumab, targets and interferes with this interaction, thereby restoring T-cell ability to remove cancer cells...

Immune checkpoint blockade is a rapidly expanding therapeutic modality in oncology. However, its adverse effects extend beyond the cytotoxicity of conventional chemotherapy. Pneumotoxicity associated with immune checkpoint therapy presents a diagnostic conundrum that has been further complicated by the COVID-19 pandemic. We report a case of a patient with metastatic urothelial carcinoma who developed diffuse alveolar hemorrhage (DAH) following treatment with avelumab.

BACKGROUND: The optimal treatment and molecular landscape of recurrent clear cell carcinoma of the vulva (VCCC) are unknown. No reported data exist regarding the efficacy of anti-programmed death 1 (PD-1) immune checkpoint inhibition in VCCC. We report on a patient with chemotherapy-refractory recurrent VCCC, who was found to have high tumor programmed death-ligand 1 (PD-L1) combined positive score (CPS), and subsequently experienced a durable partial response (PR), after treatment with off-label fifth-line pembrolizumab...