Combined sublethal irradiation and agonist anti-CD40 enhance donor T cell accumulation and control of autochthonous murine pancreatic tumors

AbstractTumor-reactive T lymphocytes can promote the regression of established tumors. However, their efficacy is often limited by immunosuppressive mechanisms that block T cell accumulation or function. ACT provides the opportunity to ameliorate immune suppression prior to transfer of tumor-reactive T cells to improve the therapeutic benefit. We evaluated the combination of lymphodepleting whole body irradiation (WBI) and agonist anti-CD40 ( αCD40) antibody on control of established autochthonous murine neuroendocrine pancreatic tumors following the transfer of naïve tumor-specific CD8 T cells. Sublethal WBI had little impact on disease outcome but did promote T cell persistence in the lymphoid organs. Host conditioning with αCD40, a n approach known to enhance APC function and T cell expansion, transiently increased donor T cell accumulation in the lymphoid organs and pancreas, but failed to control tumor progression. In contrast, combined WBI and αCD40 prolonged T cell proliferation and dramatically enhanced accumulation of d onor T cells in both the lymphoid organs and pancreas. This dual conditioning approach also promoted high levels of inflammation in the pancreas and tumor, induced histological regression of established tumors, and extended the lifespan of treated mice. Prolonged survival was entirely dependent upon adoptive transfer, but only partially dependent upon IFNγ production by donor T cells. Our results identify the novel combina...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research

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Yicheng Ni Cancer remains a major cause of death globally. Given its relapsing and fatal features, curing cancer seems to be something hardly possible for the majority of patients. In view of the development in cancer therapies, this article summarizes currently available cancer therapeutics and cure potential by cancer type and stage at diagnosis, based on literature and database reviews. Currently common cancer therapeutics include surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy. However, treatment with curative intent by these methods are mainly eligible for patients with localized diseas...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
AbstractInterferon-stimulated gene 15 (ISG15) is a 15  kDa protein induced by type I interferons (IFN-α and IFN-β) and is a member of the ubiquitin-like superfamily of proteins. The ISG15 pathway is highly expressed in various malignancies, including pancreatic ductal adenocarcinoma (PDAC), suggesting a potential role of the ISG15 pathway (free ISG1 5 and ISG15 conjugates) in pancreatic carcinogenesis. However, very little is known about how the ISG15 pathway may contribute to pancreatic tumorigenesis. In the current study, we demonstrate that ISG15 pathway knockdown reverses the KRAS-associated phenotypes ...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
Conditions:   Pancreatic Adenocarcinoma;   Pancreatic Cancer Intervention:   Biological: Autologous DC vaccine Sponsors:   Baylor College of Medicine;   Cancer Cures for Kids Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Nature Reviews Clinical Oncology, Published online: 08 November 2019; doi:10.1038/s41571-019-0281-6Virtually all patients with resectable pancreatic ductal adenocarcinoma (PDAC) will have disease progression, which is generally associated with dismal outcomes. However, novel targeted therapies and immunotherapies, selected based on the genomic and/or clinical features of patients’ tumours are beginning to improve the outcomes in subsets of patients. In this Review, the authors describe progress in novel therapies for patients with PDAC.
Source: Nature Reviews Clinical Oncology - Category: Cancer & Oncology Authors: Source Type: research
-Chuan Hung Both gemcitabine and fluoropyrimidine are recommended backbones in the first-line treatment of pancreatic ductal adenocarcinoma (PDAC). To compare the efficacy and safety of these two therapeutic backbones, and to investigate the optimal therapies, we conducted a network meta-analysis. By retrospective analysis of randomized controlled trials (RCT), the most preferred therapeutic regimen may be predicted. The eligible RCTs of the gemcitabine-based therapies and fluoropyrimidine-based therapies were searched up to 31 August 2019. In a frequentist network meta-analysis, treatments were compared and ranked acc...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
ConclusionsWe provide evidence that the treatment with immunostimulatory RNA reprograms the TME of pancreatic cancer by reducing the suppressive activity of MDSC, polarizing myeloid cells into a M1-like state and recruiting DC. We postulate that tumor cell-targeting combination strategies may benefit from RLH-based TME remodeling. In addition, we provide novel insights into the dual role of IFN signaling in MDSC ’s suppressive function and provide evidence that host-intrinsic IFN signaling may be critical for MDSC to gain suppressive function during tumor development.
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
Conclusion: NM600 is a theranostic agent with a unique ability to selectively target a variety of cancer types, presenting a unique opportunity for PET image–guided targeted radionuclide therapy and combination with immunotherapies.
Source: Journal of Nuclear Medicine - Category: Nuclear Medicine Authors: Tags: Basic Source Type: research
In this study, we investigated the cytotoxicity of plasma-treated phosphate-buffered saline (pPBS) using three PSC lines and four PCC lines and examined the immunogenicity of the induced cell death. We observed a decrease in the viability of PSC and PCC after pPBS treatment, with a higher efficacy in the latter. Two PCC lines expressed and released damage-associated molecular patterns characteristic of the induction of immunogenic cell death (ICD). In addition, pPBS-treated PCC were highly phagocytosed by dendritic cells (DCs), resulting in the maturation of DC. This indicates the high potential of pPBS to trigger ICD. In ...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Publication date: Available online 17 October 2019Source: Pathology - Research and PracticeAuthor(s): Jia Yang, Junjie Shangguan, Aydin Eresen, Yu Lia, Jian Wang, Zhuoli ZhangAbstractDespite significant advances over the past decades of research, pancreatic cancer (PC) continues to have the worst 5-year survival of any malignancy. Dendritic cells (DCs) are the most potent professional antigen-presenting cells and are involved in the induction and regulation of antitumor immune responses. DC-based immunotherapy has been used in clinical trials for PC. Although safety, efficacy, and immune activation were reported in patient...
Source: Pathology Research and Practice - Category: Pathology Source Type: research
Abstract Despite significant advances over the past decades of research, pancreatic cancer (PC) continues to have the worst 5-year survival of any malignancy. Dendritic cells (DCs) are the most potent professional antigen-presenting cells and are involved in the induction and regulation of antitumor immune responses. DC-based immunotherapy has been used in clinical trials for PC. Although safety, efficacy, and immune activation were reported in patients with PC, DC vaccines have not yet fulfilled their promise. Additional strategies for combinatorial approaches aimed to augment and sustain the antitumor specific i...
Source: Pathology, Research and Practice - Category: Pathology Authors: Tags: Pathol Res Pract Source Type: research
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