Highlights of Immunomodulation in Salmonella-Based Cancer Therapy.
Ontology highlight
ABSTRACT:
SUBMITTER: Pangilinan CR
PROVIDER: S-EPMC8615479 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Presently, cancer is one of the leading causes of death in the world, primarily due to tumor heterogeneity associated with high-grade malignancy. Tumor heterogeneity poses a tremendous challenge, especially with the emergence of resistance not only to chemo- and radiation- therapies, but also to immunotherapy using monoclonal antibodies. The use of Salmonella, as a highly selective and penetrative antitumor agent, has shown convincing results, thus meriting further investigation. In this review, the mechanisms used by Salmonella in combating cancer are carefully explained. In essence, Salmonella overcomes the suppressive nature of the tumor microenvironment and coaxes the activation of tumor-specific immune cells to induce cell death by apoptosis and autophagy. Furthermore, Salmonella treatment suppresses tumor aggressive behavior via inhibition of angiogenesis and delay of metastatic activity. Thus, harnessing the natural potential of Salmonella in eliminating tumors will provide an avenue for the development of a promising micro-based therapeutic agent that could be further enhanced to address a wide range of tumor types.
| S-EPMC6630963 | biostudies-literature
Project description:Pancreatic cancer has a high mortality rate, and its incidence is increasing worldwide. The almost universal poor prognosis of pancreatic cancer is partly due to symptoms presenting only at late stages and limited effective treatments. Recently, immune checkpoint blockade inhibitors have drastically improved patient survival in metastatic and advanced settings in certain cancers. Unfortunately, these therapies are ineffective in pancreatic cancer. However, tumor biopsies from long-term survivors of pancreatic cancer are more likely to be infiltrated by cytotoxic T-cells and certain species of bacteria that activate T-cells. These observations suggest that T-cell activation is essential for anti-tumor immunity in pancreatic cancers. This review discusses the immunological mechanisms responsible for effective anti-tumor immunity and how immune-based strategies can be exploited to develop new pancreatic cancer treatments.
| S-EPMC7696309 | biostudies-literature
Project description:Hepatocellular carcinoma (HCC) is the fastest growing malignancy in the United States in relation to mortality. HCC relies on a complex immunosuppressive network to modify the host immune system and evade destruction. Intrinsic to the liver's function and anatomy, native hepatic and immune cells produce many inhibitory cytokines that promote tolerogenicity and limit immune response. Since the introduction of sorafenib in 2008, no treatment has been able to demonstrate improved survival in patients with advanced HCC post disease progression treated with sorafenib. More recent studies have shown that sorafenib has an immunomodulatory function in addition to inhibition of multiple tyrosine kinases. Clinical trials have aimed to further enhance this immunomodulatory function with other treatments, most promisingly immune checkpoint inhibitors. Additionally, ongoing studies are using combinatorial approaches with immunomodulatory treatment and liver directed therapies such as transarterial chemoembolization (TACE), radiofrequency ablation (RFA), microwave ablation (MWA), and cryoablation. This article will review recent data describing the immunosuppressive network in HCC, recent results of immunotherapies, and combinatorial approaches to treat advanced HCC.
| S-EPMC5848038 | biostudies-literature
Project description:Intraoperative radiation therapy (IORT) delivers a single accelerated radiation dose directly to the breast tumor bed. The synergistic effects of simultaneous surgery and radiation are poorly understood. We here explored the cellular and molecular changes induced by IORT in the tumor bed compared to no-IORT exposed breast tissues. Squamous metaplasia (SM) was identified in both cohorts; however, squamous metaplasia with atypia (SMwA) was only seen in IORT specimens (63.6%, p=0.004). SMwA mimicked DCIS on histology, requiring confirmatory stains (i.e., estrogen receptor and p63) for diagnosis. Neither SM nor SMwA were found in the initial BCS specimen. We identified 1,662 differentially expressed genes (875 upregulated and 787 downregulated) between IORT and non-IORT samples. Gene ontology analyses showed that IORT was associated with the enrichment of several immune response pathways, such as inflammatory response, granulocyte activation, and T-cell activation (p<0.001). Notably, when only considering normal tissue from both cohorts, IORT was associated with intrinsic apoptotic signaling (p<0.001). Finally, we inferred a higher abundance of gamma delta T-cells, dendritic cells, and monocytes in the IORT samples compared to non-IORT samples. In conclusion, IORT induces histological changes, including squamous metaplasia with atypia, and elicits molecular alterations associated with intrinsic apoptotic signaling and immune response pathways. The higher abundance of immune-related components in breast tissue exposed to IORT suggests a potential shift towards active immunogenicity in traditionally considered immune-desert tumors such as HR-positive/HER2-negative breast cancer.
2024-04-14 | GSE253650 | GEO
Project description:Combination chemotherapy has been a mainstay in cancer treatment for the last 60 years. Although the mechanisms of action and signaling pathways affected by most treatments with single antineoplastic agents might be relatively well understood, most combinations remain poorly understood. This review presents the most common alterations of signaling pathways in response to cytotoxic and targeted anticancer drug treatments, with a discussion of how the knowledge of signaling pathways might support and orient the development of innovative strategies for anticancer combination therapy. The ultimate goal is to highlight possible strategies of chemotherapy combinations based on the signaling pathways associated with the resistance mechanisms against anticancer drugs to maximize the selective induction of cancer cell death. We consider this review an extensive compilation of updated known information on chemotherapy resistance mechanisms to promote new combination therapies to be to discussed and tested.
| S-EPMC6770082 | biostudies-other
Project description:Current modalities of cancer treatment have limitations related to poor target selectivity, resistance to treatment, and low response rates in patients. Accumulating evidence over the past few decades has demonstrated the capacity of several strains of bacteria to exert anti-tumor activities. Salmonella is the most extensively studied entity in bacterial-mediated cancer therapy, and has a good potential to induce direct tumor cell killing and manipulate the immune components of the tumor microenvironment in favor of tumor inhibition. In addition, Salmonella possesses some advantages over other approaches of cancer therapy, including high tumor specificity, deep tissue penetration, and engineering plasticity. These aspects underscore the potential of utilizing Salmonella in combination with other cancer therapeutics to improve treatment effectiveness. Herein, we describe the advantages that make Salmonella a good candidate for combination cancer therapy and summarize the findings of representative studies that aimed to investigate the therapeutic outcome of combination therapies involving Salmonella. We also highlight issues associated with their application in clinical use.
| S-EPMC8269432 | biostudies-literature
Project description:Invasive fungal disease (IFD) causes significant morbidity in immunocompromised patients due to their weakened immune system. Immunomodulatory therapy, in synergy with existing antifungal therapy, is an attractive option to enhance their immune system and aid clearance of these opportunistic pathogens. From a scientific and clinical perspective, we explore the immunotherapeutic options to augment standard antifungal drugs for patients with an IFD. We discuss the range of immunomodulatory therapies being considered in IFD - from cytokines, including G-CSF, GM-CSF, M-CSF, IFN-γ, and cytokine agonists, to cellular therapies, consisting of granulocyte transfusion, adoptive T-cell, CAR T-cell, natural killer cell therapies, and monoclonal antibodies. Adjunct pharmaceutical agents which augment the immunity are also being considered. Lastly, we explore the likelihood of the use of probiotics and manipulation of the microbiome/mycobiome to enhance IFD treatment outcomes.
| S-EPMC6068232 | biostudies-literature
Project description:Immunotherapy holds great promise in overcoming the limitations of conventional regimens for cancer therapeutics. There is growing interest among researchers and clinicians to develop novel immune-strategies for cancer diagnosis and treatment with better specificity and lesser adversity. Immunomodulation-based cancer therapies are rapidly emerging as an alternative approach that employs the host's own defense mechanisms to recognize and selectively eliminate cancerous cells. Recent advances in nanotechnology have pioneered a revolution in the field of cancer therapy. Several nanomaterials (NMs) have been utilized to surmount the challenges of conventional anti-cancer treatments like cytotoxic chemotherapy, radiation, and surgery. NMs offer a plethora of exceptional features such as a large surface area to volume ratio, effective loading, and controlled release of active drugs, tunable dimensions, and high stability. Moreover, they also possess the inherent property of interacting with living cells and altering the immune responses. However, the interaction between NMs and the immune system can give rise to unanticipated adverse reactions such as inflammation, necrosis, and hypersensitivity. Therefore, to ensure a successful and safe clinical application of immunomodulatory nanomaterials, it is imperative to acquire in-depth knowledge and a clear understanding of the complex nature of the interactions between NMs and the immune system. This review is aimed at providing an overview of the recent developments, achievements, and challenges in the application of immunomodulatory nanomaterials (iNMs) for cancer therapeutics with a focus on elucidating the mechanisms involved in the interplay between NMs and the host's immune system.
| S-EPMC7940769 | biostudies-literature
Project description:The vision of a precision medicine-guided approach to novel cancer drug development is challenged by high intratumor heterogeneity and interpatient diversity. This complexity is rarely modeled accurately during preclinical drug development, hampering predictions of clinical drug efficacy. To address this issue, we developed Comparative In Vivo Oncology (CIVO) arrayed microinjection technology to test tumor responsiveness to simultaneous microdoses of multiple drugs directly in a patient's tumor. Here, in a study of 18 canine patients with soft tissue sarcoma (STS), CIVO captured complex, patient-specific tumor responses encompassing both cancer cells and multiple immune infiltrates following localized exposure to different chemotherapy agents. CIVO also classified patient-specific tumor resistance to the most effective agent, doxorubicin, and further enabled assessment of a preclinical autophagy inhibitor, PS-1001, to reverse doxorubicin resistance. In a CIVO-identified subset of doxorubicin-resistant tumors, PS-1001 resulted in enhanced antitumor activity, increased infiltration of macrophages, and skewed this infiltrate toward M1 polarization. The ability to evaluate and cross-compare multiple drugs and drug combinations simultaneously in living tumors and across a diverse immunocompetent patient population may provide a foundation from which to make informed drug development decisions. This method also represents a viable functional approach to complement current precision oncology strategies. Cancer Res; 77(11); 2869-80. ©2017 AACR.
| S-EPMC5546104 | biostudies-other
Project description:Summary To realize the potential to use micro/nanorobots for targeted cancer therapy, it is important to improve their biocompatibility and targeting ability. Here, we report on drug-loaded magnetic microrobots capable of polarizing macrophages into the antitumor phenotype to target and inhibit cancer cells. In vitro tests demonstrated that the microrobots have good biocompatibility with normal cells and immune cells. Positively charged DOX was loaded onto the surface of microrobots via electrostatic interactions and exhibited pH-responsive release behavior. The nano-smooth surfaces of the microrobots activated M1 polarization of macrophages, thus activating their intrinsic targeting and antitumor abilities toward cancer cells. Through dual targeting from magnetic guidance and M1 macrophages, the microrobots were able to target and kill cancer cells in a 3D tumor spheroid culture assay. These findings demonstrate a way to improve the tumor-targeting and antitumor abilities of microrobots through the combined use of magnetic control, macrophages, and pH-responsive drug release. Graphical abstract Highlights • Drug-loaded achiral magnetic microrobots developed with scalability and mass fabrication• Magnetic microrobot with nano-smooth surface can activate antitumor phenotype macrophage• The magnetic targeting and targeted therapy of polarized macrophages were combined• The magnetic microrobots exhibit enhanced tumor-targeting and antitumor capabilities Drug delivery system; Biological sciences; Immunology; Biotechnology; Cancer
| S-EPMC9201018 | biostudies-literature