Cytokine & Growth Factor Reviews最新文献

The COVID-19 pandemic poses a significant challenge for individuals with compromised immune systems, such as patients with cancer, as they face a heightened susceptibility to severe infections compared to the general population. Such severe infections substantially increase the risk of morbidity and mortality among these patients. Notable risk factors for mortality include advanced age (> 70 years), current or past smoking history, advanced disease stage, the use of cytotoxic chemotherapy, and an Eastern Cooperative Oncology Group (ECOG) score of 2 or higher. Multiple types of vaccines have been developed and implemented, demonstrating remarkable efficacy in preventing infections. However, there have been observable reductions in their ability to elicit an immune response, particularly among individuals with hematological malignancies. The situation becomes more challenging due to the emergence of viral variants of concern (VOCs). Despite the increase in neutralizing antibody levels after vaccination, they remain lower in response to these evolving variants. The need for booster vaccinations has become apparent, particularly for this vulnerable population, due to the suboptimal immune response and waning of immunity post-vaccination. Examining and comprehending how the immune system reacts to various vaccination regimens for SARS-CoV-2 and its VOCs in cancer patients is crucial for designing clinical and public health strategies. This review aims to provide an updated overview of the effectiveness of COVID-19 vaccines in cancer patients, including those undergoing treatments such as hematopoietic stem cell transplantation (HCT) or chimeric antigen receptor (CAR) T cell therapy, by exploring the extent of both humoral and cellular immune responses to COVID-19 vaccination. Furthermore, it outlines risk factors and potential biomarkers that are associated with severe SARS-CoV-2 infection and vaccine responses, and offers suggestions for improving SARS-CoV-2 protection in cancer patients.

Hepatocellular carcinoma (HCC) is one of the most common gastrointestinal malignancies, characterized by insidious onset and high propensity for metastasis and recurrence. Apart from surgical resection, there are no effective curative methods for HCC in recent years, due to resistance to radiotherapy and chemotherapy. Heat shock proteins (HSP) play a crucial role in maintaining cellular homeostasis and normal organism development as molecular chaperones for intracellular proteins. Both basic research and clinical data have shown that HSPs are crucial participants in the HCC microenvironment, as well as the occurrence, development, metastasis, and resistance to radiotherapy and chemotherapy in various malignancies, particularly liver cancer. This review aims to discuss the molecular mechanisms and potential clinical value of HSPs in HCC, which may provide new insights for HSP-based therapeutic interventions for HCC.

CD40 is a member of the tumor necrosis factor (TNF) receptor superfamily of receptors expressed on a variety of cell types. The CD40–CD40L interaction gives rise to many immune events, including the licensing of dendritic cells to activate CD8⁺ effector T cells, as well as the facilitation of B cell activation, proliferation, and differentiation. In malignant cells, the expression of CD40 varies among cancer types, mediating cellular proliferation, apoptosis, survival and the secretion of cytokines and chemokines. Agonistic human anti-CD40 antibodies are emerging as an option for cancer treatment, and early-phase clinical trials explored its monotherapy or combination with radiotherapy, chemotherapy, immune checkpoint blockade, and other immunomodulatory approaches. In this review, we present the current understanding of the mechanism of action for CD40, along with results from the clinical development of agonistic human CD40 antibodies in cancer treatment (selicrelumab, CDX-1140, APX005M, mitazalimab, 2141-V11, SEA-CD40, LVGN7409, and bispecific antibodies). This review also examines the safety profile of CD40 agonists in both preclinical and clinical settings, highlighting optimized dosage levels, potential adverse effects, and strategies to mitigate them.

Ferroptosis is a type of cell death characterized by iron-dependent phospholipid peroxidation and reactive oxygen species overproduction. Ferroptosis induces immunogenic cell death and elicits anti-tumor immune responses, playing an important role in cancer immunotherapy. Ferroptosis suppression in cancer cells impairs its immunotherapeutic efficacy. To overcome this issue, ferroptosis inducers (FINs) have been combined with other cancer therapies to create an anti-tumor immune microenvironment. However, the ferroptosis-based crosstalk between immune and tumor cells is complex because oxidative products released by ferroptotic tumor cells impair the functions of anti-tumor immune cells, resulting in immunotherapeutic resistance. In the present article, we have reviewed ferroptosis in tumor and immune cells and summarized the crosstalk between ferroptotic tumor cells and the immune microenvironment. Based on the existing literature, we have further discussed future perspectives on opportunities for combining ferroptosis-targeted therapies with cancer immunotherapies.

Uterine fibroids (UF), also called uterine leiomyoma, is one of the most prevalent uterine tumors. UF represents a serious women's health global problem with a significant physical, emotional, and socioeconomic impact. Risk factors for UF include racial disparities, age, race, hormonal factors, obesity, and lifestyle (diet, physical activity, and stress. There are several biological contributors to UF pathogenesis such as cellular proliferation, angiogenesis, and extracellular matrix (ECM) accumulation. This review addresses tumor immune microenvironment as a novel mediator of ECM deposition. Polarization of immune microenvironment towards the immunosuppressive phenotype has been associated with ECM deposition. Immunosuppressive cells include M2 macrophage, myeloid-derived suppressor cells (MDSCs), and Th17 cells, and their secretomes include interleukin 4 (IL-4), IL-10, IL-13, IL-17, IL-22, arginase 1, and transforming growth factor-beta (TGF-β1). The change in the immune microenvironment not only increase tumor growth but also aids in collagen synthesis and ECM disposition, which is one of the main hallmarks of UF pathogenesis. This review invites further investigations on the change in the UF immune microenvironment as well as a novel targeting approach instead of the traditional UF hormonal and supportive treatment.

In contemporary oncology, radiation therapy and immunotherapy stand as critical treatments, each with distinct mechanisms and outcomes. Radiation therapy, a key player in cancer management, targets cancer cells by damaging their DNA with ionizing radiation. Its effectiveness is heightened when used alongside other treatments like surgery and chemotherapy. Employing varied radiation types like X-rays, gamma rays, and proton beams, this approach aims to minimize damage to healthy tissue. However, it is not without risks, including potential damage to surrounding normal cells and side effects ranging from skin inflammation to serious long-term complications. Conversely, immunotherapy marks a revolutionary step in cancer treatment, leveraging the body’s immune system to target and destroy cancer cells. It manipulates the immune system’s specificity and memory, offering a versatile approach either alone or in combination with other treatments. Immunotherapy is known for its targeted action, long-lasting responses, and fewer side effects compared to traditional therapies. The interaction between radiation therapy and immunotherapy is intricate, with potential for both synergistic and antagonistic effects. Their combined use can be more effective than either treatment alone, but careful consideration of timing and sequence is essential. This review explores the impact of various radiation therapy regimens on immunotherapy, focusing on changes in the immune microenvironment, immune protein expression, and epigenetic factors, emphasizing the need for personalized treatment strategies and ongoing research to enhance the efficacy of these combined therapies in cancer care.

This concise review navigates the intricate realm of Interleukin-6 (IL-6), an important member of the cytokine family. Beginning with an introduction to cytokines, this narrative review unfolds with the historical journey of IL-6, illuminating its evolving significance. A crucial section unravels the three distinct signaling modes employed by IL-6, providing a foundational understanding of its versatile interactions within cellular landscapes. Moving deeper, the review meticulously dissects IL-6's signaling mechanisms, unraveling the complexities of its pleiotropic effects in both physiological responses and pathological conditions. A significant focus is dedicated to the essential role IL-6 plays in inflammatory diseases, offering insights into its associations and implications for various health conditions. The review also takes a therapeutic turn by exploring the emergence of anti-IL-6 monoclonal inhibitors, marking a profound stride in treatment modalities. Diving into the molecular realm, the review explores small molecules as agents for IL-6 inhibition, providing a nuanced perspective on diverse intervention strategies. As the review embarks on the final chapters, it contemplates future aspects, offering glimpses into potential research trajectories and the evolving landscape of IL-6-related studies.

The imbalance between proliferation and death of kidney resident cells is a crucial factor in the development of acute or chronic renal dysfunction. Acute kidney injury (AKI) is often associated with the rapid loss of tubular epithelial cells (TECs). Sustained injury leads to the loss of glomerular endothelial cells (GECs) and podocytes, which is a key mechanism in the pathogenesis of glomerular diseases. This irreversible damage resulting from progressive cell loss eventually leads to deterioration of renal function characterized by glomerular compensatory hypertrophy, tubular degeneration, and renal fibrosis. Regulated cell death (RCD), which involves a cascade of gene expression events with tight structures, plays a certain role in regulating kidney health by determining the fate of kidney resident cells. Under pathological conditions, cells in the nephron have been demonstrated to constitutively release extracellular vesicles (EVs) which act as messengers that specifically interact with recipient cells to regulate their cell death process. For therapeutic intervention, exogenous EVs have exhibited great potential for the prevention and treatment of kidney disease by modulating RCD, with enhanced effects through engineering modification. Based on the functional role of EVs, this review comprehensively explores the regulation of RCD by EVs in AKI and chronic kidney disease (CKD), with emphasis on pathogenesis and therapeutic intervention.

Myeloid-derived growth factor (MYDGF) is a paracrine protein produced by bone marrow-derived monocytes and macrophages. Current research shows that it has protective effects on the cardiovascular system, such as repairing heart tissue after myocardial infarction, enhancing cardiomyocyte proliferation, improving cardiac regeneration after myocardial injury, regulating proliferation and survival of endothelial cells, reducing endothelial cell damage, resisting pressure overload-induced heart failure, as well as protecting against atherosclerosis. Furthermore, regarding the metabolic diseases, MYDGF has effects of improving type 2 diabetes mellitus, relieving non-alcoholic fatty liver disease, alleviating glomerular diseases, and resisting osteoporosis. Herein, we will discuss the biology of MYDGF and its effects on cardiovascular and metabolic diseases.

Cell-to-cell communication mediated by Extracellular Vesicles (EVs) is a novel and emerging area of research, especially during pregnancy, in which placenta derived EVs can facilitate the feto-maternal communication. EVs comprise a heterogeneous group of vesicle sub-populations with diverse physical and biochemical characteristics and originate by specific biogenesis mechanisms. EVs transfer molecular cargo (including proteins, nucleic acids, and lipids) between cells and are critical mediators of cell communication. There is growing interest among researchers to explore into the molecular cargo of EVs and their functions in a physiological and pathological context. For example, inflammatory mediators such as cytokines are shown to be released in EVs and EVs derived from immune cells play key roles in mediating the immune response as well as immunoregulatory pathways. Pregnancy complications such as gestational diabetes mellitus, preeclampsia, intrauterine growth restriction and preterm birth are associated with altered levels of circulating EVs, with differential EV cargo and bioactivity in target cells. This implicates the intriguing roles of EVs in reprogramming the maternal physiology during pregnancy. Moreover, the capacity of EVs to carry bioactive molecules makes them a promising tool for biomarker development and targeted therapies in pregnancy complications. This review summarizes the physiological and pathological roles played by EVs in pregnancy and pregnancy-related disorders and describes the potential of EVs to be translated into clinical applications in the diagnosis and treatment of pregnancy complications.