Glioblastoma (GBM) is the most common malignancy of the central nervous system in adults. GBM has high levels of therapy failure and its prognosis is usually dismal. The phenotypic heterogeneity of the tumor cells, dynamic complexity of non-tumor cell populations within the GBM tumor microenvironment (TME), and their bi-directional cross-talk contribute to the challenges of current therapeutic approaches. Herein, we discuss the etiology of GBM, and describe several major types of non-tumor cells within its TME, their impact on GBM pathogenesis, and molecular mechanisms of such an impact. We also discuss their value as potential therapeutic targets or prognostic biomarkers, with reference to the most recent works on this subject. We conclude that unless all “key player” populations of non-tumor cells within the TME are considered, no breakthrough in developing treatment for GBM can be achieved.
Introduction. Lung cancer is the leading cause of cancer mortality in men and women. Due to its high prevalence and significant recurrence rate after standard therapy, the search for new methods of lung cancer treating is an urgent task. A promising treatment strategy is immunotherapy that elicit immune response against tumor cells.Objective. Evaluation of the clinical efficacy and prospects for the safe use of immunotherapy in malignant neoplasms of the pleural cavity.Discussion. The introduction of immunotherapeutic approaches, including adoptive cell therapy with tumor-infiltrating lymphocytes (TIL) or CAR-T cells, the development of neoantigen vaccines, oncolytic viruses, in combination with chemotherapy and blockade of immune checkpoints (ICP) have shown optimistic results in preclinical studies and are currently at different stages of clinical trials for safety and efficacy.Conclusions. Immunotherapy of lung cancer is a promising area of adjuvant therapy. For clinical introduction, immunotherapeutic approaches should be further investigated to increase their effectiveness and minimizing side effects by combining different therapies, improving bioengineered and cellular drugs, and reducing the cost of treatment.
“Lung-on-a-chip” (LoC) is a microfluidic device, imitating the gas-fluid interface of the pulmonary alveole in the human lung and intended for pathophysiological, pharmacological and molecular-biological studies of the air-blood barrier in vitro. The LoC device itself contains a system of fluid and gas microchannels, separated with a semipermeable elastic membrane, containing a polymer base and the alveolar cell elements. Depending on the type of LoC (single-, double- and three-channel), the membrane may contain only alveolocytes or alveolocytes combined with other cells — endotheliocytes, fibroblasts, alveolar macrophages or tumor cells. Some LoC models also include proteinic or hydrogel stroma, imitating the pulmonary interstitium. The first double-channel LoC variant, in which one side of the membrane contained an alveolocytic monolayer and the other side — a monolayer of endotheliocytes, was developed in 2010 by a group of scientists from the Harvard University for maximally precise in vitro reproduction of the micro-environment and biomechanics operations of the alveoli. Modern LoC modifications include the same elements and differ only by the construction of the microfluidic system, by the biomaterial of semipermeable membrane, by the composition of cellular and stromal elements and by specific tasks to be solved. Besides the LoC imitating the hematoalveolar barrier, there are modifications for studying the specific pathophysiological processes, for the screening of medicinal products, for modeling specific diseases, for example, lung cancer, chronic obstructive pulmonary disease or asthma. In the present review, we have analyzed the existing types of LoC, the biomaterials used, the methods of detecting molecular processes within the microfluidic devices and the main directions of research to be conducted using the “lung-on-a-chip”.