International review of cell and molecular biology最新文献

The advent of immunotherapy in cancer has provided new avenues in the treatment of many malignancies at various stages. Specifically, immune checkpoint inhibitors (ICIs) have transformed the field of lung cancer treatment. However, since some tumors can evade the immune system, not all patients respond properly. Recent research has provided evidence showing how microRNAs (miRNAs) are involved in regulating many immune checkpoints. MiRNAs have demonstrated their ability to modulate immune evasion of tumor cells. Currently, reliable markers are being sought to predict the efficacy of immunotherapy in these types of cancers. Therefore, the association of serum miRNAs and the response of ICIs in lung cancer is under study. Many miRNA molecules and their corresponding target genes have been identified in the regulation of chemoresistance. Therefore, elucidating how these miRNAs control the function of immune checkpoints, as well as the effectiveness of therapies based on ICIs set the basis for the development of new biomarkers to predict treatment response to ICIs. This chapter delves into the molecular role of miRNAs interacting with ICs, such as PD-1 and PD-L1, and the clinical utility of miRNAs, such as miR-16, miR-146a, and miR-335, in predicting treatment response to ICI-based therapy in lung cancer. The aim is to provide a deep insight of the current landscape, serving as a cornerstone for further research.

The increasing prevalence of breast cancer presents a significant global health challenge, highlighting the urgent need for improved diagnostic and treatment monitoring methods. The non-invasive nature of cell-free circulating epigenomic biomarkers, such as methylated DNA (metDNA) and microRNAs (miRNAs), offers a reassuring approach to identifying breast cancer patients in the early stages and assessing their response to therapy. This approach holds great promise for diagnosis and treatment evaluation, prioritizing patient comfort and well-being. Cell-free circulating metDNA and miRNAs are released into the bloodstream from dying tumor cells through apoptosis and necrosis, carrying tumor-specific genetic and epigenetic changes. These changes encompass alterations in DNA methylation patterns, are pivotal in regulating gene expression, and are frequently disrupted in cancer. The interplay between these processes and the dynamic release of epigenomic biomarkers provides a real-time snapshot of the genetic and epigenetic features of the tumor. Integrating the analysis of metDNA and miRNA biomarkers into clinical practice can facilitate the early detection of breast cancer and improve the precision of treatment monitoring. By tracking changes in these biological markers, healthcare professionals can make informed decisions regarding modifications to therapy, ultimately enhancing patient outcomes. Gaining insights into the underlying mechanisms of cell-free circulating epigenomic biomarkers offers a groundbreaking approach to diagnosing and treating breast cancer.

Head and neck squamous cell carcinoma (HNSCC) is a prevalent and aggressive malignant tumor with poor clinical prognosis. The immune system plays a critical role in tumor surveillance and response to therapy. Among various immune cell populations, γδ T (γδ T) cells, a unique subset of lymphocytes, have emerged as significant participants in the anti-tumor immune response and have attracted extensive attention in recent studies. This chapter discusses the unique properties of γδ T cells, their role in HNSCC, and evaluates their potential value as therapeutic targets for HNSCC.

The human microbiome consists of the diverse microorganisms with their equally diverse functional abilities that have evolved over millions of years with humans. This microbiome creates a mutually beneficial symbiotic relationship with their host. Through their varied functions, the human gut microbiota is crucial for preserving health and homeostasis. Any imbalance in this microbial population can lead to an array of diseased states, including cancer especially of the gastrointestinal system. The focus of this chapter is to discuss the mechanisms through which the gut microbiome creates a conducive environment for initiation and progression of cancer. In addition, the effect of microbial products such as short chain fatty acids, bile acids and Trimethylamine N-oxide on the formation of gastrointestinal cancer is also discussed. The various experimental methods and new molecular techniques that have facilitated the characterization and study of microorganisms is also discussed. The developments in microbiome research have shed light on the potential role of gut microbiota for novel biomarker discovery and therapeutic interventions in gastrointestinal cancer, like fecal microbiota transplantation. The prospects of these areas for further exploration are discussed.

Cytokines play a dynamic crucial role in orchestrating homeostasis, immune responses, and the hallmarks and enabling characteristics of cancer cells, particularly by promoting tumor-inflammation and facilitating cancer immune evasion. By dysregulating cytokine production or hijacking signaling pathways, intrinsically or extrinsically, cancer cells can create an immunosuppressive tumor microenvironment that enables them to escape anti-tumor immune responses and promote survival, tumor growth, angiogenesis, metastasis and resistance to anticancer therapies, particularly immunotherapies. Despite extensive research, significant gaps remain in our understanding of cytokines, due to their pleiotropic and context-dependent nature, which varies based on cell type, tissue environment, and cytokine balance. While cytokines are typically classified as pro-inflammatory or immunosuppressive, most of them can act in both ways. Targeting cytokine signaling pathways holds substantial clinical potential, serving as prognostic and predictive biomarkers of response, and therapeutic targets that could improve anti-tumor outcomes, as demonstrated in various preclinical and clinical studies, either as monotherapy or in combination with anticancer therapies, including immunotherapies. For this reason, research focused on their understanding, particularly in how cytokines reshape the tumor microenvironment and the development of therapeutic strategies that target cytokine signaling has garnered increasing attention from the scientific community in recent years. In this review, we will describe the central role of cytokines in cancer, focusing on cytokine-driven mechanisms that contribute to the suppression of anti-tumor immune responses. We will uncover how cancer cells can exploit cytokine signaling pathways to dampen the immune response, promote tumor growth, facilitate metastasis, and enable resistance to anticancer therapies. Key cytokines, such as TGF-β, IL-10, LIF, VEGF, IFNγ, IL-2, IL-12, IL-1, IL-6, IL-8 and TNF-α will be described for their central role in cancer and immune evasion. Furthermore, we will discuss strategies aimed at targeting these cytokines signaling pathways as promising approaches that can improve anti-tumor immune responses and clinical outcomes, particularly in combination with cancer immunotherapies.

Cytokines are crucial modulators of immune responses and have emerged as key components in cancer immunotherapy, particularly concerning Natural Killer (NK) cells. Indeed, the administration of these cytokines have demonstrated significant therapeutic potential in clinical settings. For instance, interleukin-2 (IL-2) has shown efficacy in melanoma and renal cell carcinoma, enhancing anti-tumor immunity but often associated with dose-limiting toxicities. IL-12 has been linked to improved survival rates in various solid tumors by stimulating Th1 responses and activating NK cells. Additionally, IL-15 has gained recognition for its ability to enhance NK cell proliferation and persistence, translating into favorable clinical outcomes in hematological malignancies such as acute myeloid leukemia (AML). Remarkably, cytokines can act synergistically providing stronger effects, and recent advancements have led to the identification of cytokine-induced memory-like NK (CIML-NK) cells. Despite these advancements, significant challenges persist in the translation of cytokine and NK cell therapies into routine clinical practice. The short half-life of recombinant cytokines poses limitations on their effectiveness, requiring high doses that can lead to severe side effects. Additionally, the complexities involved in the large-scale production of cytokines and the development of GMP-grade NK cell-therapies must be overcome. Innovative delivery systems, such as heterodimeric fusion proteins, oncolytic viruses and cytokine gene therapy, have emerged to address these issues, yet further research is needed to optimize these approaches. Collectively, this review underscores the importance of cytokines in harnessing the full potential of NK cells for cancer immunotherapy, and ongoing efforts that aim to optimize cytokine delivery strategies and enhance NK cell manufacturing processes.

Gamma delta (γδ) T lymphocytes are a heterogeneous population of immune cells that correspond between 1 % and 5 % of mice lymphoid tissues and human blood lymphocytes. However, their prevalence increases markedly in epithelial and mucosal tissues such as the skin. The ability of γδ T cells to rapidly produce cytokines positions them as key contributors in the early stages of immune response. For this reason, γδ T cells bridge innate and adaptive immunity, thus regulating early stages of inflammatory processes, wound healing, and defence against pathogens and tumours. Remarkably, γδ T cells are also involved in the pathogenesis of skin autoimmune diseases such as psoriasis, atopic dermatitis and alopecia areata. This chapter addresses the involvement of several γδ T cell subsets in these inflammatory skin diseases, focusing on their ontogeny and functional phenotypes, in both mouse and human skin.

This chapter examines the intricate relationship between gamma-delta (γδ) T cells and cellular stress pathways in the context of emerging infectious diseases. γδ T cells, a distinct subset of lymphocytes, are integral to the innate immune response, as they can recognize a diverse array of antigens independently of Major Histocompatibility Complex (MHC) restriction. They function as initial sentinels, secreting cytokines, and cytotoxic molecules to directly eradicate infected cells and regulate the immune system. This chapter examines the activation mechanisms of γδ T cells in response to viral infectious agents such as Influenza A virus, SARS-CoV-2, West Nile Virus (WNV), Dengue virus, and Human immunodeficiency virus (HIV) emphasizing their role in pathogen control and disease progression. The document examines cellular stress pathways, specifically the unfolded protein response (UPR) and integrated stress response (ISR), which are frequently activated by pathogens. These pathways initiate protective mechanisms; however, their dysregulation may lead to pathological conditions. The chapter examines the mechanisms by which certain pathogens utilize host stress responses to enhance replication and evade immune detection. The impact of stress on γδ T cell functionality and immune responses is examined. The document examines the potential of γδ T cell-based therapies for diverse infections, highlighting the necessity for additional research to enhance delivery methods and reduce the risk of autoimmune disorders. Comprehending these interactions is essential for formulating innovative approaches to prevent and treat emerging infectious diseases.