International review of cell and molecular biology最新文献

Therapeutic monoclonal antibodies blocking different immune checkpoints, have demonstrated efficacy against a wide variety of solid tumors. The exclusion or absence of lymphocytes within the tumor microenvironment (TME) is one of the main resistance mechanisms to immune checkpoint inhibitor (ICI)-based therapies. Therefore, there is a growing interest in identifying novel approaches to promote T cell infiltration on immune-deserted (cold) and immune-excluded tumors to turn them into inflamed (hot) tumors. Here, we provide a comprehensive overview of the recently published studies showing the potential of low-dose radiation (LDRT) to reprogram the TME to allow and promote T-cell infiltration and thus, improve currently approved ICI-based therapies.

Myeloid-derived suppressor cells (MDSCs) are a group of heterogenous immature myeloid cells with potent immune suppressive properties that not only constrain anti-tumor immune activation and functions, promote tumor progression, but also contribute to treatment resistance and tumor relapse. Targeting MDSCs may be a promising new cancer treatment method, but there is still a problem of low treatment efficiency. Combined application with radiotherapy may be a potential method to solve this problem. Drug delivery systems (DDSs) provide more efficient targeted drug delivery capability and can reduce the toxicity and side effects of drugs. Recent advance in DDSs targeting development, recruitment, differentiation, and elimination of MDSCs have shown promising effect in reversing immune inhibition and in overcoming radiotherapy resistance. In this review, we systematically summarized DDSs applied to target MDSCs for the first time, and classified and discussed it according to its different mechanisms of action. In addition, this paper also reviewed the biological characteristics of MDSCs and their role in the initiation, progression, and metastasis of cancer. Moreover, this review also summarizes the role of DDSs targeting MDSCs in radiosensitization. Finally, the future development of DDSs targeting MDSCs is also prospected.

Activating and recruiting the immune system is critical for successful cancer treatment. Since the discovery of immune checkpoint inhibitors, immunotherapy has become the standard of care for many types of cancers. However, many patients fail to respond to immunotherapy. Further research is needed to understand the mechanisms of resistance and adjuvant therapies that can help sensitize patients to immunotherapies. Here, we will discuss how radiotherapy can change the tumor microenvironment and work synergistically with immunotherapy. We will examine different pre-clinical models focusing on their limitations and their unique advantages in studying the efficacy of treatments and the tumor microenvironment. We will also describe emerging findings from clinical trials testing the combination of immunotherapy and radiotherapy.

Natural killer (NK) cells are innate lymphoid cells that play an essential role in the anti-tumor response through immunosurveillance, multiple mechanisms of cytotoxicity and the synthesis of cytokines modulating the immune tumor microenvironment (TME). After the dramatic advances in immunotherapy targeting T cells including the success of checkpoint inhibitors or autologous chimeric antigen receptor (CAR) expressing T cells in clinical practice, NK cells have gained growing interest for the development of new therapies. Although NK cells have shown promising responses in leukemia patients, the effects of NK-targeted therapies are currently limited in the treatment of solid tumors. Thus, radiotherapy could provide a valuable solution to improve treatments targeting NK cells. Indeed, ionizing radiations represent a powerful immuno-modulator that can either induce a pro-inflammatory and anti-tumor TME, or conversely lead to immunosuppression of effector immune cells in favor of tumor growth and therapeutic escape, depending on how it is delivered and tumor models. However, the effects of ionizing radiation on NK cells are only partially understood. Therefore, we review the effects of radiotherapy on the NK cell-mediated anti-tumor response, and propose potential strategies to reinvigorate NK cells by combining radiotherapy with NK cell-targeted therapies.

Radiotherapy (RT) is a fundamental treatment at the locoregional or oligometastatic stages of cancer. In various tumors, RT effects may be optimized using synergistic combinations that enhance tumor response. Innovative strategies have been designed that explore the radiation mechanisms, at the physical, chemical and biological levels, to propose precision RT approaches. They consist in combining RT with immunotherapy to revert radiation immunosuppressive effects or to enhance radiation-induced immune defenses against the tumor to favor immunogenic cell death. Radiotherapy-activated nanoparticles are another innovation. By increasing radiation response in situ, nanoparticles improve tumor control locally, and can trigger systemic immune reactions that may be exploited to improve the systemic efficacy of RT. Strong clinical evidence of improved outcomes is now available for combinations of RT and immunotherapy on one hand and RT and nanoparticles on the other hand. The triple combination of RT, immunotherapy and nanoparticles is promising in terms of tolerance, local and systemic anti-tumor control. Yet, significant challenges remain to unravel the complexity of the multiscale mechanisms underlying response to this combination and their associated parameters. Such parameters include patient characteristics, tumor bulk and histology, radiation technique, energy, dose, fractionation, immunotherapy targets and predictive biomarkers, nanoparticle type, size, delivery (intratumoral/intravenous), distribution. The temporal combination is another critical parameter. The mechanisms of response of the combinatorial approaches are reviewed, with a focus on underlying mechanisms based on preclinical, translational and clinical studies. Opportunities for translation of current understanding into precision RT trials combined with immunotherapy and nanoparticles are also discussed.

Legionella pneumophila is the causative agent of Legionnaires' disease, a severe pneumonia. L. pneumophila injects via a type-IV-secretion-system (T4SS) more than 300 bacterial proteins into macrophages, its main host cell in humans. Certain of these bacterial effectors target organelles in the infected cell and hijack multiple processes to facilitate all steps of the intracellular life cycle of this pathogen. In this review, we discuss the interplay between L. pneumophila, an intracellular bacterium fully armed with virulence tools, and mitochondria, the extraordinary eukaryotic organelles playing prominent roles in cellular bioenergetics, cell-autonomous immunity and cell death. We present and discuss key findings concerning the multiple interactions of L. pneumophila with mitochondria during infection and the mechanisms employed by T4SS effectors that target mitochondrial functions to subvert infected cells.

This article provides an updated review on the evolution of mitochondria from bacteria, which were likely related to extant alphaproteobacteria. Particular attention is given to the timeline of oxygen history on Earth and the entwined phases of eukaryotic evolution that produced the animals that still populate our planet. Mitochondria of early-branching unicellular eukaryotes and plants appear to retain partial or vestigial traits that were directly inherited from the alphaproteobacterial ancestors of the organelles. Most of such traits define the current aerobic physiology of mitochondria. Conversely, the anaerobic traits that would be essential in the syntrophic associations postulated for the evolution of eukaryotic cells are scantly present in extant alphaproteobacteria, and therefore cannot help defining from which bacterial lineage the ancestors of mitochondria originated. This question has recently been addressed quantitatively, reaching the novel conclusion that marine bacteria related to Iodidimonas may be the living relatives of protomitochondria. Additional evidence is presented that either support or does not contrast this novel view of the bacterial origin of mitochondria.

Lung tumors are one of the most aggressive threats affecting humans. Current therapeutic approaches have improved patients' survival; however, further efforts are required to increase effectiveness and protection against tumor relapse and metastasis. Immunotherapy presents an alternative to previous treatments that focuses on stimulating of the patient's immune system to destroy tumor cells. Viruses can be used as part of the immune therapeutic approach as agents that could selectively infect tumor cells, triggering an immune response against the infection and against the tumor cells. Some viruses have been selected for specifically infecting and destroying cancer cells, activating the immune response, enhancing access, amplifying the cytotoxicity against the tumor cells, and improving the long-term memory that can prevent tumor relapse. Oncolytic virotherapy can then be used as a strategy to target the destruction of transformed cells at the tumor site and act in locations distant from the primary targeted tumor site. Some of the current challenges in lung cancer treatment can be addressed using traditional therapies combined with oncolytic virotherapy. Defining the best combination, including the choice of the right settings will be at the next frontier in lung cancer treatment.

High-grade gliomas (HGGs) are the most common and aggressive primary brain tumors in both adult and pediatric populations. Despite the multimodal treatment modality currently available for HGG, the prognosis is dismal, with a low overall survival rate at two years after diagnosis. In the last decade, oncolytic virotherapy has emerged as a promising and feasible therapeutic tool in management of these tumors due to its oncolytic and immunostimulatory properties. Various oncolytic viruses, such as herpes simplex virus, adenovirus, poliovirus, reovirus, parvovirus and others, have been evaluated in the early stages of the clinical setting with regard to improving the outcome of patients with HGG. In this review, we summarize completed and ongoing clinical trials of oncolytic virotherapy for adult and pediatric malignant gliomas in terms of safety and efficacy, followed by a brief discussion about the current status and future directions of this therapy in the brain tumor field.

Periodontal disease is one of the most common inflammatory disorders in humans. Gingivitis is the mildest form of periodontal disease and its progression can lead to periodontitis, an inflammatory disease characterized by soft tissue damage that can lead to progressive destruction of the periodontal ligament and alveolar bone. Diverse populations of immune cells are involved in periodontal disease. Myeloid-derived suppressor cells (MDSCs) represent a heterogeneous group of immature myeloid cells derived from hematopoietic precursor cells and exhibit T cell immunosuppressive functions that are thought to be involved in periodontal disease. Therefore, MDSCs have been recently analyzed in the context of this disease. In this review, we discuss the most recent advances in the characterization of the biological aspects, subpopulations, and traffic of MDSCs, as well as their immunosuppressive and osteoclastogenic activity in the context of periodontal disease and in the presence of key periodontal pathogens.