International review of cell and molecular biology最新文献

The human microbiome plays a crucial role in maintaining health and preventing disease. Dysbiosis, or imbalance, in the microbiome, has been linked to various diseases, including cancer. This chapter explores the influence of microbiomes on different organs, immune system modulation, and cancer development. Specific microorganisms, such as Helicobacter pylori, Escherichia coli, and human papillomavirus (HPV), contribute to gastric, colorectal, and cervical cancer through mechanisms like immunomodulation and proliferative signaling pathways. Dysbiosis-induced cancer progression involves NF-κB, Wnt/β-catenin, and JAK/STAT signaling. Recent studies highlight the microbiome's potential in cancer diagnosis and immunotherapy. Fecal Microbiota Transplantation (FMT) and predictive biomarkers, such as Porphyromonas gingivalis and Escherichia-Shigella, show promise in treating colorectal cancer. The microbiome influences tumor biology and immune response, affecting immunotherapeutic efficacy. Understanding microbiome-cancer interactions offers new opportunities for improved diagnosis and personalized therapy. This chapter provides comprehensive insights into the role of microbiome in cancer progression, emphasizing the importance of microbiome research in developing effective cancer treatments.

Chimeric Antigen Receptor (CAR) T-cell therapy represents a significant advancement in treating hematologic malignancies. However, its therapeutic efficacy against solid tumors remains hindered by several challenges, including suboptimal antitumor activity, high toxicity, and the emergence of resistance mechanisms. In recent years, the microbiome has emerged as a critical modulator of cancer immunotherapy outcomes. Yet, the precise molecular and cellular pathways through which the microbiome influences CAR-T cell efficacy remain largely unexplored. This chapter provides a comprehensive review of current knowledge regarding the interactions between CAR-T cell therapy and the microbiome, with particular emphasis on gut microbial dynamics. Additionally, it underscores the existing gaps in our understanding of these interactions and highlights key preclinical and clinical findings. We also discuss innovative strategies aimed at manipulating the microbiome to enhance CAR-T cell function, thereby presenting potential avenues for optimizing therapeutic outcomes.

Acute myeloid leukemia (AML) is a complex cancer, yet advances in recent years from integrated genomics methods have helped improve diagnosis, treatment, and means of patient stratification. A recent example of a powerful, multimodal method is DOGMA-seq, which can measure chromatin accessibility, gene expression, and cell-surface protein levels from the same individual cell simultaneously. Previous bimodal single-cell techniques, such as CITE-seq (Cellular indexing of transcriptomes and epitopes), have only permitted the transcriptome and cell-surface protein expression measurement. DOGMA-seq, however, builds on this foundation and has implications for examining epigenomic, transcriptomic, and proteomic interactions between various cell types. This technique has the potential to be particularly useful in the study of cancers such as AML. This is because the cellular mechanisms that drive AML are rather heterogeneous and require a more complete understanding of the interplay between the genetic mutations, disruptions in RNA transcription and translation, and surface protein expression that cause these cancers to develop and evolve. This technique will hopefully contribute to a more clear and complete understanding of the growth and progression of complex cancers.

DNA methylation is one of the best-known epigenetic markers and plays a critical role in the control of gene activity and the architecture of the nucleus of the cell. Epigenetic alterations and especially DNA methylation have a high potential to provide valuable and innovative cancer biomarkers. Liquid biopsy is a unique minimally invasive tool for the management of cancer patients based on the extraction of information through detailed molecular analysis of circulating genetic material in peripheral blood and allows us to characterize the evolution of a solid tumor in real time. DNA methylation in combination with liquid biopsy is very powerful when it comes to providing circulating epigenetic biomarkers of clinical importance. Numerous DNA methylation markers are now being tested in liquid biopsies as potential biomarkers in various types of cancer. DNA methylation is mostly being studied in ctDNA but there are also a small number of studies up to now performed in gDNA isolated from CTCs. A highly important dimension of the combination of liquid biopsy/DNA methylation analysis is its high potential for early cancer detection since alterations in DNA methylation in plasma can be detected very early during cancer pathogenesis. Methylated DNA, modified nucleosomes and noncoding RNAs can be used as blood circulating epigenetic biomarkers for real-time and minimally-invasive cancer monitoring. DNA methylation is very promising and powerful in providing novel biomarkers for improving cancer diagnostics, while another important dimension in this field is the use of DNA methylation inhibitors in cancer treatment. In this chapter we present the current findings on epigenetic alterations detected in CTCs in various types of cancer, and further discuss their potential as novel liquid biopsy-based DNA methylation biomarkers.

Circulating tumor cells (CTC), released by primary tumors into the bloodstream, represent a valuable source to inform on cancer heterogeneity, cancer progression, metastatic disease and therapy efficacy without the need of invasive tumor biopsies. However, the extreme rarity and heterogeneity of CTCs, occurring at genotypic, phenotypic and functional levels, poses a major challenge for the study of this population and explains the lack of standardized strategies of CTC isolation. Lung cancer, the leading causes of cancer-related death worldwide, is a paradigmatic example of how CTC heterogeneity can undermine the clinical utility of this biomarker, since contrasting data have been reported using different isolation technologies. Some evidences suggest that only a fraction of CTC, characterized by stem-like feature and partial epithelial-mesenchymal transition (EMT) phenotype, can sustain metastasis initiation. Cancer stem cells (CSCs) have the potential to maintain primary tumors, initiate metastasis and escape both chemotherapy and immunotherapy treatments. Moreover, a close connection has been reported in several tumor types among hybrid phenotype, characterized by retention of epithelial and mesenchymal traits, acquisition of CSC feature and increased metastatic potential. This review focuses on the phenotypic and functional heterogeneity of CTCs and the resulting implications for their isolation and clinical validation, especially in the setting of non-small cell lung cancer (NSCLC). In particular, we discuss the most relevant studies providing evidence for the presence and prognostic/predictive value of CTC subsets characterized by stem-like and hybrid EMT phenotype. Despite technical and conceptual issues, tracking circulating CSCs has the potential to improve the prognostic/predictive value of CTCs in NSCLC setting and could provide novel insights into the comprehension of the metastatic process and identification of novel therapeutic targets.

The suprachiasmatic nucleus (SCN) functions as the master circadian pacemaker in mammals. Since 2015, facilitated by cutting-edge optogenetic and chemogenetic techniques, significant progress has been made in understanding the circuits involving the SCN that mediate diverse physiological functions. The time-specific and cell type-selective manipulation of neuronal activity within and outside the SCN drove the verification of both expected and previously unrecognized circuits operating for controlling various functions, including circadian locomotor activity, itch behavior, anticipatory thirst, aggression, corticosterone release, food-anticipatory activity, wakefulness, and photoperiod-related adaptive behavior. In addition, optogenetic/chemogenetic approaches verified the functional connection of the SCN to the control of body temperature, heart rate, and insulin sensitivity through as-yet-unknown circuit details. This review intends to provide an overview of SCN input/output pathways elucidated by optogenetics and chemogenetics. A fundamental question remains regarding the coherence of the identified numerous output pathways that are dictated by the SCN. Deciphering the potential coordination among the SCN's circuits via optogenetics and chemogenetics is needed to understand the mechanism underlying the harmonious regulation of multiple circadian physiologies.

Cytokines regulate both innate and adaptive immunity, thus bridging these two types of immune response. Initially explored as standalone cancer therapies, their use was hindered by the unfavorable pharmacokinetic profiles of recombinant molecules and the competition from newer, more promising immunotherapies. However, with the advent of bioengineered cytokines featuring extended half-lives and reduced off-target effects, their therapeutic potential is being re-evaluated, especially in combination with monoclonal antibodies, immune checkpoint inhibitors, cancer vaccines, and advanced cellular therapies. Regarding cellular therapies, cytokines can be used to enhance the ex vivo expansion of therapeutic bioproducts or improve their in vivo persistence and function. In the context of allogeneic hematopoietic stem cell transplantation, cytokines may support immune reconstitution, thereby reducing the risk of serious infections and disease recurrence. The immunomodulatory role of cytokines is particularly relevant in hematolymphoid malignancies, given the rising incidence of these conditions and the increasing cumulative exposure to various classes of chemotherapeutic agents. Also, this happens in a context where there is a decline in immune function, particularly relevant in older adults and in those with other chronic illnesses. In this review, we examine recent advances in cytokine-based therapies for hematological malignancies, both as monotherapy and in combination with chemotherapeutic agents, immunomodulatory drugs, or advanced cellular therapies.

Tumor necrosis factor-alpha (TNF-α) is a proinflammatory cytokine that plays a key role in regulating immune responses. It is primarily produced by activated macrophages but also by other cell types, including T lymphocytes and natural killer (NK) cells. TNF-α is involved in many physiological processes, including cell proliferation and differentiation. Furthermore, TNF-α has been associated with the development of many inflammatory and autoimmune diseases. Recent studies have underscored the critical role of TNF-α in neuropathic pain, a complex and frequently debilitating condition resulting from nerve injury or dysfunction. Increased levels of TNF-α in the nervous system have been associated with the development of neuropathic pain, contributing to neuronal sensitization and altered pain pathways. This fact positions TNF-α as a potential therapeutic target for pain management. The efficacy of targeting TNF-α in neuropathic pain has been evaluated via preclinical and clinical models. Preclinical studies have shown that administering anti-TNF-α antibodies can reduce pain behaviors and inflammation, suggesting a promising therapeutic approach. Current clinical trials are being conducted to evaluate the effectiveness of anti-TNF-α therapies, with promising results in patients with neuropathic pain.

Allergic diseases including asthma, allergic rhinitis, food allergies, and atopic dermatitis arise from an overactive immune response following exposure to allergens. The increasing prevalence of these conditions highlights the urgent need to deepen our understanding of their underlying mechanisms to develop more effective therapeutic strategies. Recent studies have shed light on the role of γδ (γδ) T cells in allergic diseases, emphasizing their complex and context-dependent functions. Depending on the microenvironment, γδ T cells can either exacerbate or mitigate allergic inflammation, a duality attributed to the specific γδ T cell subsets involved. Although immunotherapies targeting γδ T cells have made significant advances in the field of cancer treatment, their application to allergic diseases remains in its early stages. Nevertheless, certain subsets of γδ T cells exhibit promising Type 2 helper (Th2) T lymphocytes-suppressing capabilities, which could help restore the immune balance that is disrupted in Th2-polarized allergic responses. This potential suggests that γδ T cell-based therapies could represent a viable approach for modulating immune responses in allergic diseases, offering new avenues for treatment where conventional therapies have fallen short. Future research is needed to further elucidate the therapeutic potential of γδ T cells in allergy management and to optimize their application as a novel immunotherapeutic strategy.