PD-1/ PD-L1 blockade as a novel treatment for colorectal cancer.

We present a comprehensive knowledge of immune therapy through PD-1/PD-L1 blockade that argues how efficient the process is, in colon cancer carcinoma. In this review, we discuss the responsiveness of immunotherapy on PD-1/PD-L1 blockade and various tactics for overcoming weak responses to these checkpoint inhibitors in CRC. More research using controlled trials is required to enable new discoveries to provide continued success with immune-based therapies and grounds for optimism about the future of CRC patients. PMID: 30522017 [PubMed - as supplied by publisher]
Source: Biomedicine and pharmacotherapy = Biomedecine and pharmacotherapie - Category: Drugs & Pharmacology Authors: Tags: Biomed Pharmacother Source Type: research

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Popovici V Abstract The dysfunction of the DNA mismatch repair system results in microsatellite instability (MSI). MSI plays a central role in the development of multiple human cancers. In colon cancer, despite being associated with resistance to 5-fluorouracil treatment, MSI is a favourable prognostic marker. In gastric and endometrial cancers, its prognostic value is not so well established. Nevertheless, recognising the MSI tumours may be important for predicting the therapeutic effect of immune checkpoint inhibitors. Several gene expression signatures were trained on microarray data sets to understand the reg...
Source: Biomed Res - Category: Research Authors: Tags: Biomed Res Int Source Type: research
In this study, we show that human CD4+ TEMs stimulated with CD28SA adopt a metabolic program similar to those of tumor cells with enhanced glucose utilization, lipid biosynthesis, and proliferation in hypoxic conditions. Identification of metabolic profiles underlying hyperactive T cell activation would provide a platform to test safety of immunostimulatory antibodies. PMID: 31009338 [PubMed - in process]
Source: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy - Category: Microbiology Tags: Monoclon Antib Immunodiagn Immunother Source Type: research
Authors: Kieber-Emmons T PMID: 31009337 [PubMed - in process]
Source: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy - Category: Microbiology Tags: Monoclon Antib Immunodiagn Immunother Source Type: research
In this study, we immunized mice with tigPDPN-overexpressing Chinese hamster ovary (CHO)-K1 cells (CHO/tigPDPN) and screened hybridomas producing mAbs against tigPDPN using flow cytometry. One of the mAbs, PMab-231 (IgG2a, kappa), specifically detected CHO/tigPDPN cells using flow cytometry as well as recognized tigPDPN protein using western blotting. In addition, PMab-231 was found to cross-react with cat PDPN (cPDPN). The dissociation constants (KD) of PMab-231 for CHO/tigPDPN and CHO/cPDPN cells were determined to be 1.2 × 10-8 and 1.9 × 10-8, respectively, indicating moderate aff...
Source: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy - Category: Microbiology Tags: Monoclon Antib Immunodiagn Immunother Source Type: research
Authors: Ravindranath MH, Filippone EJ, Devarajan A, Asgharzadeh S Abstract Cytotoxic NK/CD8+ T cells interact with MHC-I ligands on tumor cells through either activating or inhibiting receptors. One of the inhibitory receptors is CD94/NKG2A. The NK/CD8+ T cell cytotoxic capability is lost when tumor-associated human leukocyte antigen, HLA-E, binds the CD94/NKG2A receptor, resulting in tumor progression and reduced survival. Failure of cancer patients to respond to natural killer (NK) cell therapies could be due to HLA-E overexpression in tumor tissues. Preventing the inhibitory receptor-ligand interaction by eithe...
Source: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy - Category: Microbiology Tags: Monoclon Antib Immunodiagn Immunother Source Type: research
Markus Hartl* and Rainer Schneider Center of Molecular Biosciences (CMBI), Institute of Biochemistry, University of Innsbruck, Innsbruck, Austria The neuronal proteins GAP43 (neuromodulin), MARCKS, and BASP1 are highly expressed in the growth cones of nerve cells where they are involved in signal transmission and cytoskeleton organization. Although their primary structures are unrelated, these signaling proteins share several structural properties like fatty acid modification, and the presence of cationic effector domains. GAP43, MARCKS, and BASP1 bind to cell membrane phospholipids, a process reversibly regulate...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
In this study, several biopsies from a patient-derived primary renal-cell carcinoma were analyzed by whole-exome sequencing and aligned to healthy tissue. Next to several shared mutations between different subclones, ca. 23% of the mutations were only found in specific regions of the tumor. Strikingly, a single biopsy of that same tumor only covered around 55% of the total mutational diversity, underlining the need for multi-region sampling. Tracing the order of mutations in different subclones revealed that they develop in a branching fashion from the primary tumor clone, harboring the driver mutation, rather than in a li...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
In this study, T cells deficient in TRAF6 display enhanced T cell activation, CD28-indpendent stimulation and resistance to Treg cell-mediated suppression (176). Although TLR signaling can promote T cell resistance to Treg cells, the precise molecular mechanism remains yet to be elucidated. It is worth noting that TLR stimulation of T cells increases cytokine production (173, 177), thus future studies should delineate the effect of TLR-MyD88 signaling vs. subsequently induced cytokines in generating resistance to Treg cells. Lastly, it is also crucial to evaluate the effect of TLR signaling on regulatory T cells which also...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
We present a comprehensive knowledge of immune therapy through PD-1/PD-L1 blockade that argues how efficient the process is, in colon cancer carcinoma. In this review, we discuss the responsiveness of immunotherapy on PD-1/PD-L1 blockade and various tactics for overcoming weak responses to these checkpoint inhibitors in CRC. More research using controlled trials is required to enable new discoveries to provide continued success with immune-based therapies and grounds for optimism about the future of CRC patients.Graphical abstractThe mechanism of interaction between PD-1+ T-cells and PD-L1/2+ tumor cells.
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research
Programmed death ligand 1 (PD-L1) expressed on the tumour cell surface, or on neighbouring host immune cells in the tumour microenvironment, engages the programmed death 1 (PD-1) receptor on activated cytotoxic T cells and thus downregulates the tumour-directed host immune response. Dismantling of this negative feedback loop is at the core of novel cancer immunotherapeutic strategies. Anti-PD-1 and anti-PD-L1 immune checkpoint inhibitors have shown good efficacy against several types of solid tumours in patients with advanced melanoma, non-small-cell lung cancer, renal cell carcinoma, and some types of colon cancer.
Source: LANCET - Category: Journals (General) Authors: Tags: Comment Source Type: research
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