Polysaccharide enhanced NK cell cytotoxicity against pancreatic cancer via TLR4/MAPKs/NF-κB pathway in vitro/vivo

Publication date: Available online 20 August 2019Source: Carbohydrate PolymersAuthor(s): Xin Xie, Lingman Ma, Yiran Zhou, Wen Shen, Duiyue Xu, Jie Dou, Baiyong Shen, Changlin ZhouAbstractA polysaccharide isolated from Strongylocentrotus nudus eggs (SEP) reportedly displays immune activity in vivo. Here, its effect and underlying mechanism in the treatment of pancreatic cancer were investigated. SEP obviously inhibited pancreatic cancer growth by activating NK cells in vitro/vivo via TLR4/MAPKs/NF-κB signaling pathway, The tumor inhibitory rate achieved to 44.5% and 50.8% at a dose of 40 mg/kg in Bxpc-3 and SW1990 nude mice, respectively. Moreover, SEP obviously augmented the Gemcitabine (GEM) antitumor effect by upregulating NKG2D, which improved the sensitivity of NK cells targeting to its ligand MICA; meanwhile, the antitumor inhibitory rate was 68.6% in BxPC-3 tumor-bearing mice,. Moreover, SEP reversed GEM-induced apoptosis and atrophy in both spleen and bone marrow via suppressing ROS secretion in vivo. These results suggested that pancreatic cancer was effectively inhibited by SEP-enhanced NK cytotoxicity mediated primarily through TLR4/MAPKs/NF-κB signaling pathway, representing a potential immunotherapy candidate for the treatment of pancreatic cancer.
Source: Carbohydrate Polymers - Category: Biomedical Science Source Type: research

Related Links:

Nature Reviews Clinical Oncology, Published online: 17 September 2019; doi:10.1038/s41571-019-0276-3The presence and prognostic relevance of the intratumoural microbiota in pancreatic cancer, and the roles of intratumoural bacteria in oncogenesis and therapeutic response are beginning to be elucidated. The feasibility of characterizing intratumoural microbial communities from paraffin-embedded tissues has now been validated, providing greater opportunities for retrospective research. Prospective studies are also needed to test the efficacy of rational approaches combining microbial modulation with chemotherapy and/or immunotherapy.
Source: Nature Reviews Clinical Oncology - Category: Cancer & Oncology Authors: Source Type: research
We performed a prospective immunohistochemical analysis of lymphocyte activation gene 3 (LAG3) for 430 consecutive patients with advanced gastrointestinal, genitourinary, or rare cancers between June 2012 and March 2016. Most patients (428/430, 99.5%) were evaluable for LAG3 expression by immunohistochemistry. In total, 18.5% (79/428) of the evaluated cancers expressed LAG3, including pancreatic cancer (33.3%, 2/6), gastric cancer (24.7%, 21/85), colorectal cancer (23.6%, 48/203), melanoma (12.5%, 1/8), genitourinary cancer (9.5%, 4/46), biliary tract cancer (6.3%, 1/16), and sarcoma (5.4%, 2/37), but not miscellaneous (0....
Source: Journal of Immunotherapy - Category: Allergy & Immunology Tags: Basic Studies Source Type: research
In this study, HER2 and MUC1-based peptides were synthesized and preclinically evaluated in an effort to develop peptide-based SPECT radiopharmaceuticals derived from tumor-associated antigens for the detection of breast cancer. Our findings demonstrate that the tumor antigen peptides radiolabeled efficiently with 99mTc and showed high metabolic stability in human plasma in vitro. The data from breast tumor cell binding confirmed the high affinity (in low nanomolar range) towards respective breast cancer cell lines. In healthy mice, 99mTc-labeled peptides displayed favorable pharmacokinetics, with high excretion by the ren...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research
In this study, we performed immunohistochemistry to detect the PD-L2, CD3, CD8, transforming growth factor- β2 (TGF-β2) and FOXP3 levels in paraffin sections from 305 patients with resected PDAC as a training set. Expression levels of intratumoral and stromal immune markers were compared in relation to survival using Kaplan-Meier curves, random survival forest model and survival tree analysis. A multiva riable Cox proportional-hazards model of associated markers was used to calculate the risk scores.ResultsPD-L2 was expressed in 71.5% of PDAC samples and showed strong correlations with CD3+, CD8+ T cells and FOXP...
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
ConclusionIn contrast to traditional therapy, DC-CIK immunotherapy not only shows improved short-term effect, long-term effect and immunologic function, but also reduces mortality and negative immunoregulatory index, and shows mild adverse reactions. This is the first study to evaluate the clinical effect and safety of DC-CIK immunotherapy for PC, and it indicated that DC-CIK immunotherapy may be suitable for patients with advanced PC or intolerance to radiotherapy and chemotherapy.
Source: Cytotherapy - Category: Cytology Source Type: research
CONCLUSIONS: Combining an anti-PD-1 antibody, nivolumab, with a Treg-depleting anti-CCR4 antibody, mogamulizumab, provides an acceptable safety profile, antitumor activity, and a potentially effective option in cancer immunotherapy. PMID: 31455681 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
AbstractImmunotherapy has led to a paradigm shift in the treatment of many advanced malignancies. Despite the success in treatment of tumors like non-small cell lung cancer (NSCLC) and melanoma, checkpoint inhibition-based immunotherapy has limitations. Many tumors, such as pancreatic cancer, are less responsive to checkpoint inhibitors, where patients tend to have a limited duration of benefit and where clinical responses are more robust in patients who are positive for predictive biomarkers. One of the critical factors that influence the efficacy of immunotherapy is the tumor microenvironment (TME), which contains a hete...
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
Publication date: 20 August 2019Source: Cell Reports, Volume 28, Issue 8Author(s): Adam L. Burrack, Ellen J. Spartz, Jackson F. Raynor, Iris Wang, Margaret Olson, Ingunn M. StromnesSummaryPancreatic ductal adenocarcinoma (PDA) is a lethal cancer resistant to immunotherapy. We create a PDA mouse model and show that neoantigen expression is required for intratumoral T cell accumulation and response to immune checkpoint blockade. By generating a peptide:MHC tetramer, we identify that PDA induces rapid intratumoral, and progressive systemic, tumor-specific T cell exhaustion. Monotherapy PD-1 or PD-L1 blockade enhance...
Source: Cell Reports - Category: Cytology Source Type: research
This study suggests that inhibition of the cancer promoting effects of gastrin in pancreatic cancer can decrease metastases by altering the tumor microenvironment (TME) and decreasing pathways that activate the epithelial mesenchymal transition (EMT). PAS vaccine appears to change the tumor microenvironment, making it more susceptible to therapy with an immune checkpoint antibody. This novel combination of two immunotherapies may improve survival of pancreatic cancer by decreasing both tumor growth and metastasis formation. PMID: 31433212 [PubMed - as supplied by publisher]
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - Category: Physiology Authors: Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research
It is good to see that more of the promising technical approaches to aspects of aging, originally put forward by people in the SENS rejuvenation research network some years ago, are now making solid progress towards commercial implementation. The LIFT, or GIFT, approach to cancer therapy involves the transplantation of suitably aggressive leukocyte or granulocyte immune cells from a donor. At the time it was first demonstrated to be highly effective in mice, more than a decade ago, the underlying mechanisms were not well explored, and that always makes it hard to obtain further support from scientific funding institutions....
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs
More News: Biomedical Science | Cancer | Cancer & Oncology | Carbohydrates | Immunotherapy | Pancreas | Pancreatic Cancer