Despite advances in diagnostics and therapy of non-small cell lung cancer (NSCLC), the problem of prognosis and prevention of tumor progression is still highly important. Even if NSCLC is diagnosed in the early stages, almost a quarter of patients develop relapse; most of them die from recurrent disease. A large number of different markers have been proposed to predict the risk of NSCLC progression; however, none of them are used in clinical practice. It is obvious that this situation is related to the economic and methodological complexity of the proposed markers and/or their insufficient efficiency due to a lack of effective study models and tumor heterogeneity. Another reason may be that potential markers are developed for NSCLC progression in general, which is represented by at least four pathogenetically-distinct processes: synchronous lymph node metastasis, local, regional, and distant recurrence. In this review, we summarize data from published literature on clinicopathological, genetic, and molecular factors associated with different types of NSCLC progression and emphasize challenges and approaches to developing prognostic factors. In conclusion, we highlight the importance of further studies to reveal molecular mechanisms of NSCLC progression and the need for differential analysis of markers of local, regional, and distant recurrences for disease prognosis.
Summary. Macrophages are important effectors of innate immunity and the key component of the tumor microenvironment strongly influencing cancer disease outcome and efficiency of cancer therapy. Moreover, recent data have shown that monocytes as macrophage precursors can impact on tumor ability to progression. It’s well known that although tumor-associated macrophages consist of diverse populations, in general, they have tumor-supporting activity. To change tumor-supporting state of tumor-associated macrophages toward tumor-inhibiting mode is one of prospective aims of modern cancer immunotherapy. Cytostatics seems to be possible tools to achieve this aim, because recently it has been shown that chemo- and radiotherapy possess immunomodulatory effects. Most of the findings are related to lymphocytes — T-lymphocytes and NK-cells, but not to monocyte/macrophage lineage. In the review, we have analyzed how cytostatic drugs influence the properties of monocyte/macrophage lineage cells to prospect using of chemotherapy to enhance their antitumor activity.
Macrophages are key components of the innate immune system. The variability of the macrophage’s participation in tumor progression, determined by their functional polarization, opens up a wide prospect for modulating their functional profile, primarily in the direction of increasing antitumor activity. The purpose of the study was to provide up-to-date data on the process of macrophage polarization, mechanisms of its regulation, polarization markers and induction factors. Material and methods. A search was made for available literature sources published in Web of Science, Scopus and other databases. more than 160 sources devoted to the study of the process of macrophage polarization were found, of which 121 were included in this review. Results. This review presents data on the molecular mechanisms and gene signatures associated with M1 and M2 polarization of macrophages. We displayed information on metabolic, phenotypic characteristics and cytokine profile of M1- and M2-macrophages, as well as highlighted data on polarization factors and targets of their action. Conclusion. The information presented in the review can serve as an information base for the development of experimental and clinical approaches for editing the functional profile of macrophages in order to control their involvement in various pathological processes.
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