scholarly journals The Glycolytic Pathway as a Target for Novel Onco-Immunology Therapies in Pancreatic Cancer

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1642
Author(s):  
Claudia Curcio ◽  
Silvia Brugiapaglia ◽  
Sara Bulfamante ◽  
Laura Follia ◽  
Paola Cappello ◽  
...  
Keyword(s):  
Antitumor Immunity ◽  
Human Cancer ◽  
Treatment Resistance ◽  
Glycolytic Enzymes ◽  
Ductal Adenocarcinoma ◽  
Cellular Immune Responses ◽  
Altered Glucose ◽  
Hypoxic Tumor ◽  
Cellular Immune ◽  
Glycolytic Rate

Pancreatic ductal adenocarcinoma (PDA) is one of the most lethal forms of human cancer, characterized by unrestrained progression, invasiveness and treatment resistance. To date, there are limited curative options, with surgical resection as the only effective strategy, hence the urgent need to discover novel therapies. A platform of onco-immunology targets is represented by molecules that play a role in the reprogrammed cellular metabolism as one hallmark of cancer. Due to the hypoxic tumor microenvironment (TME), PDA cells display an altered glucose metabolism—resulting in its increased uptake—and a higher glycolytic rate, which leads to lactate accumulation and them acting as fuel for cancer cells. The consequent acidification of the TME results in immunosuppression, which impairs the antitumor immunity. This review analyzes the genetic background and the emerging glycolytic enzymes that are involved in tumor progression, development and metastasis, and how this represents feasible therapeutic targets to counteract PDA. In particular, as the overexpressed or mutated glycolytic enzymes stimulate both humoral and cellular immune responses, we will discuss their possible exploitation as immunological targets in anti-PDA therapeutic strategies.

scholarly journals Induction of Robust and Specific Humoral and Cellular Immune Responses by Bovine Viral Diarrhea Virus Virus-Like Particles (BVDV-VLPs) Engineered with Baculovirus Expression Vector System

Vaccines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 350
Author(s):  
Zhanhui Wang ◽  
Mengyao Liu ◽  
Haoran Zhao ◽  
Pengpeng Wang ◽  
Wenge Ma ◽  
...  
Keyword(s):  
Immune Responses ◽  
Vector System ◽  
Baculovirus Expression Vector System ◽  
Diarrhea Virus ◽  
Viral Diarrhea ◽  
Cellular Immune Responses ◽  
Baculovirus Expression ◽  
Baculovirus Expression Vector ◽  
Cellular Immune ◽  
Viral Diarrhea Virus

Bovine viral diarrhea virus (BVDV) is an important animal pathogen that affects cattle. Infections caused by the virus have resulted in substantial economic losses and outbreaks of BVDV are reported globally. Virus-like particles (VLPs) are promising vaccine technology largely due to their safety and strong ability to elicit robust immune responses. In this study, we developed a strategy to generate BVDV-VLPs using a baculovirus expression vector system (BEVS). We were able to assemble BVDV-VLPs composed of dimerized viral proteins E2 and Erns, and the VLPs were spherical particles with the diameters of about 50 nm. Mice immunized with 15 μg of VLPs adjuvanted with ISA201 elicited higher levels of E2-specific IgG, IgG1, and IgG2a antibodies as well as higher BVDV-neutralizing activity in comparison with controls. Re-stimulation of the splenocytes collected from mice immunized with VLPs led to significantly increased levels of CD3+CD4+T cells and CD3+CD8+T cells. In addition, the splenocytes showed dramatically enhanced proliferation and the secretion of Th1-associated IFN-γ and Th2-associated IL-4 compared to that of the unstimulated control group. Taken together, our data indicate that BVDV-VLPs efficiently induced BVDV-specific humoral and cellular immune responses in mice, showing a promising potential of developing BVDV-VLP-based vaccines for the prevention of BVDV infections.

scholarly journals Dynamic Stromal Alterations Influence Tumor-Stroma Crosstalk to Promote Pancreatic Cancer and Treatment Resistance

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3481
Author(s):  
Kendelle J. Murphy ◽  
Cecilia R. Chambers ◽  
David Herrmann ◽  
Paul Timpson ◽  
Brooke A. Pereira
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Development ◽  
Treatment Resistance ◽  
Tumor Stroma ◽  
Response To Treatment ◽  
Ductal Adenocarcinoma ◽  
Cell Phenotype ◽  
Stromal Compartment ◽  
Clinical Prognosis ◽  
Functional Value

Many cancer studies now recognize that disease initiation, progression, and response to treatment are strongly influenced by the microenvironmental niche. Widespread desmoplasia, or fibrosis, is fundamental to pancreatic cancer development, growth, metastasis, and treatment resistance. This fibrotic landscape is largely regulated by cancer-associated fibroblasts (CAFs), which deposit and remodel extracellular matrix (ECM) in the tumor microenvironment (TME). This review will explore the prognostic and functional value of the stromal compartment in predicting outcomes and clinical prognosis in pancreatic ductal adenocarcinoma (PDAC). We will also discuss the major dynamic stromal alterations that occur in the pancreatic TME during tumor development and progression, and how the stromal ECM can influence cancer cell phenotype, metabolism, and immune response from a biochemical and biomechanical viewpoint. Lastly, we will provide an outlook on the latest clinical advances in the field of anti-fibrotic co-targeting in combination with chemotherapy or immunotherapy in PDAC, providing insight into the current challenges in treating this highly aggressive, fibrotic malignancy.

scholarly journals Implementation of Adenovirus-Mediated Pulmonary Expression of Human ACE2 in HLA Transgenic Mice Enables Establishment of a COVID-19 Murine Model for Assessment of Immune Responses to SARS-CoV-2 Infection

Pathogens ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 940
Author(s):  
Theodor Chitlaru ◽  
Erez Bar-Haim ◽  
Liat Bar-On ◽  
Shahar Rotem ◽  
Hila Cohen ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Immune Responses ◽  
Post Infection ◽  
High Reproducibility ◽  
Cellular Immune Responses ◽  
Loss Of Weight ◽  
Transient Loss ◽  
Different Strains ◽  
Cellular Immune ◽  
Human Specific

HLA transgenic mice are instrumental for evaluation of human-specific immune responses to viral infection. Mice do not develop COVID-19 upon infection with SARS-CoV-2 due to the strict tropism of the virus to the human ACE2 receptor. The aim of the current study was the implementation of an adenovirus-mediated infection protocol for human ACE2 expression in HLA transgenic mice. Transient pulmonary expression of the human ACE2 receptor in these mice results in their sensitisation to SARS-CoV-2 infection, consequently providing a valuable animal model for COVID-19. Infection results in a transient loss in body weight starting 3 days post-infection, reaching 20–30% loss of weight at day 7 and full recovery at days 11–13 post-infection. The evolution of the disease revealed high reproducibility and very low variability among individual mice. The method was implemented in two different strains of HLA immunized mice. Infected animals developed strong protective humoral and cellular immune responses specific to the viral spike-protein, strictly depending on the adenovirus-mediated human ACE2 expression. Convalescent animals were protected against a subsequent re-infection with SARS-CoV-2, demonstrating that the model may be applied for assessment of efficacy of anti-viral immune responses.

Sign in / Sign up

Export Citation Format

Share Document