Ovarian cancer is the deadliest malignant tumor in the female reproductive system. Despite advancements in standard treatments such as tumor debulking surgery and platinum-based chemotherapy, the overall survival rate remains low. The emergence of targeted therapies, including Poly(ADP-ribose) polymerase (PARP) inhibitors and anti-angiogenic agents, has provided new avenues for treatment. However, drug resistance and disease heterogeneity continue to pose significant challenges. Immune checkpoint inhibitors (ICIs), as an emerging therapeutic approach, primarily target the programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4) pathways to restore anti-tumor immune responses. Although ICIs have shown significant efficacy in other malignancies, their effectiveness in ovarian cancer is limited, with a response rate of only 10–15% for monotherapy. Recent studies have focused on combining ICIs with chemotherapy, anti-angiogenic agents, or PARP inhibitors to enhance therapeutic outcomes. This article reviews the progress of ICIs in ovarian cancer, including monotherapy and combination treatment strategies, and explores emerging therapeutic targets and strategies aimed at improving patient prognosis and achieving personalized treatment. By gaining a deeper understanding of the tumor microenvironment and its immune evasion mechanisms, there is hope for developing more effective treatment options in the future, ultimately improving the survival rates and quality of life for ovarian cancer patients.

The efficacy of chimeric antigen receptor (CAR)-T therapy may not match initial expectations due to the influence of multiple circumstances, some of which cannot be predicted. CAR-T treatment groups include high-risk patients, particularly those with TP53 mutations. A significant body of research has demonstrated that mutations in the TP53 gene play a pivotal role in cancer development and progression. Any aberration in the TP53 gene in cancer is invariably associated with complications and a poor prognosis. Moreover, mutations in the TP53 gene have been observed to correlate with resistance to conventional chemotherapy, prompting the use of alternative therapeutic approaches, including CAR-T therapy. However, there is a possibility that abnormalities in the TP53 gene may affect patients after CAR-T cell administration reducing the efficacy of therapy. This review examines the link between TP53 mutations in cancer and the efficacy of CAR-T therapy, as well as the potential implications of this aspect in therapeutic planning.

Cancer-related pain represents one of the most common complaints of cancer patients especially for those with advanced-stage of disease and/or bone metastases. More effective therapeutic strategies are needed not only to improve the survival of cancer patients but also to relieve cancer-related pain. In the last decade, immune checkpoint inhibitor (ICI)-based immunotherapy targeting programmed cell death-1 (PD-1) and its ligand 1 (PD-L1) has revolutionized cancer care. Beyond its anticancer role, PD-1/PD-L1 axis pathway is involved in many other physiological processes. PD-L1 expression is found in both malignant tissues and normal tissues including the dorsal root ganglion, and spinal cord. Through its interaction with PD-1, PD-L1 can modulate neuron excitability, leading to the suppression of inflammatory, neuropathic, and bone cancer pain. Therefore, since the intricate relationship between immunotherapy and pain should be largely dissected, this comprehensive review explores the complex relationship between PD-1/PD-L1-based immunotherapy and cancer-related pain. It delves into the potential mechanisms through which PD-1/PD-L1 immunotherapy might modulate pain pathways, including neuroinflammation, neuromodulation, opioid mechanisms, and bone processes. Understanding these mechanisms is crucial for developing future research directions in order to optimize pain management strategies in cancer patients. Finally, this article discusses the role of artificial intelligence (AI) in advancing research and clinical practice in this context. AI-based strategies, such as analyzing large datasets and creating predictive models, can identify patterns and correlations between PD-1/PD-L1 immunotherapy and pain. These tools can assist healthcare providers in tailoring treatment plans and pain management strategies to individual patients, ultimately improving outcomes and quality of life for those undergoing PD-1/PD-L1-based immunotherapy.

The tripartite network, including the nervous, immune, and endocrine systems, plays a significant role in regulatory and effector processes in the male body. On the one hand, males perform their reproduction function by generating spermatozoa in conditions of self-tolerance maintenance because most spermatozoa antigens (“sequestrated antigens”) are unknown to the immune system. On the other hand, in everyday life, a male body encounters hostile external infections, some of which colonize the skin and barrier surfaces and present a cancer threat to male genital tracts. This is human papillomavirus (HPV), the “silent killer”. Therefore, the male immune system has to function in a contradictory situation using either active immune responses, self-tolerance mechanisms, or both simultaneously. This review focused on the functional organization of the male immune system, including its coordination with the nervous and endocrine systems, and immune processes at the level of the whole organism, as well as on obvious changes, which have currently happened. The male immune system should function in conditions of the strong influence of testosterone and biosocial impulses coming from the nervous system. In the last century, researchers obtained data showing a decrease in the male reproduction function because of a stable negative dynamic of spermatozoa count and quality. Nowadays, depressing statistical indicators of male fertility have been published. 15% of couples are unable to conceive a child, where 50% of the causes of infertility relate to males, and up to 15% of male infertility cases are due to immunological disorders. It can be assumed that the male immune system starts to function when self-tolerance is partially lost, and the previous balance has been destroyed. Furthermore, sperm allergy has become a new topic in male immunology.

Immunotherapy, a primary anti-neoplastic treatment, exploits the patient’s immune system to kill neoplastic cells by modulating immune checkpoints such as cytotoxic T-lymphocyte antigen 4 and programmed cell death 1. Despite an apparent anti-neoplastic efficacy, immunotherapeutic agents are often accompanied by multiorgan toxicity, including gastrointestinal ones. This particular class of immunotherapy-related adverse events, mainly represented by diarrhea and colitis, necessitates a nuanced treatment strategy. Current treatments are primarily based on standardized severity grading systems to guide and proportion therapeutic interventions, ranging from simple behavioral modifications or conventional molecules (such as anti-diarrheal) to advanced biological treatments. Tofacitinib, a pan-Janus kinase inhibitor, emerged as a potential option for managing immune-related (IR) colitis by targeting hyperactivated T cells within the colic microenvironment. However, evidence supporting the use of tofacitinib in IR colitis is primarily derived from case reports and small case series, lacking robust randomized clinical trial data. While preliminary findings demonstrate encouraging clinical control of IR colitis with tofacitinib, further research is warranted to elucidate its efficacy, safety, optimal dosage, and treatment duration. Although there are some worries about its effects on cancer response and safety, current evidence indicates that tofacitinib could be seen as a possible treatment choice if other therapies with more robust evidence profiles have not been successful.

The complement system is a key component of the innate immune system that mediates the clearance of pathogens, apoptotic cells, and cellular debris. However, the complement system also has diverse roles in the central nervous system (CNS), where it regulates synaptic pruning, neural plasticity, and neuroinflammation. Dysregulation of the complement system has been implicated in various neurodegenerative disorders such as Alzheimer’s disease, multiple sclerosis, epilepsy, stroke, and traumatic brain injury. In these conditions, excessive or chronic activation of the complement system may lead to synaptic loss, neuronal damage, immune dysregulation, and inflammation, which leads to exacerbating the disease’s progression and severity. Moreover, the complement system may interact with infectious agents that invade the CNS, such as bacteria, viruses, fungi, and parasites, and modulate their pathogenicity and host response. Therefore, understanding the complex interplay between the complement system and the CNS is crucial for developing novel therapeutic strategies to prevent or treat neurodegenerative and neuroimmune disorders. Natural compounds, such as plant extracts, phytochemicals, and nutraceuticals, have emerged as promising candidates for modulating the complement system and its effects on the CNS. These compounds may exert anti-inflammatory, antioxidant, neuroprotective, and immunomodulatory effects by regulating the expression of various complement components and pathways. In this review, we summarized the current knowledge on the roles of the complement system in human neurodegenerative disorders and the benefits of natural compounds for complement-targeted therapy.

The narrative review aims to shed light on the influence of inflammation in the comorbid chronic pain and major depressive disorder (MDD). This connection is known to be multifactorial, with a dynamic interaction between genetic and epigenetic factors. However, a growing body of evidence has shown that the co-presence of MDD and pain is underlain by immune mechanisms involved in the persistence of the inflammatory process. In particular, the cytokines released following activation of the innate immune system during inflammation cause changes at the endocrine level that result in glucocorticoid resistance, as well as altering the synthesis and metabolism of some central nervous system (CNS) mediators. Cytokines appear to generate neuroinflammation by activating normally protective microglia. Various other mechanisms, including changes in the function of the glutamatergic, GABAergic, and serotonergic systems are also implicated, but inflammation-induced reduction of BDNF (brain-derived neurotrophic factor) appears to be the deciding factor. In turn, neuroinflammation leads to sickness behavior, which is characterized by anhedonia and social withdrawal. This review explored these mechanisms, which may be at the root of comorbid pain and MDD. Although intriguing, however, most available evidence comes from animal studies, and rigorous clinical exploration is warranted.

Measles virus (Morbillivirus abbreviated as MV, but more recently MeV) is the causal agent of measles disease, thought to have existed at least 4,000 years ago, affecting predominantly infants, but also immunocompromised individuals remaining a public health issue today globally. In this review, we discuss the historical background about MeV infection to modern-day research on measles disease, current epidemiology, but also what is known about immunisation against it. We report what is known about the viral structure and the function of the viral proteins. This additionally covers the cellular structure of MeV, mechanisms, and clinical aspects of infection. Including a review of topics like cellular receptor-associated entry factors, to the immunology of MeV infection. In this review, the current knowledge of innate immune responses during infection is explained, which involves changes to chemokine and cytokine expression, finalised by the present understanding of adaptive immune responses to MeV. The genomic stability of the MeV proteins is explained and suggestive that it could be the third pathogen with eradication potential (after the variola and rinderpest viruses). Further biological and immunological clarification as to how this could occur is explained below.

Primary biliary cholangitis (PBC) is a rare immune-mediated disease, commonly affecting women in their 40s, and ultimately progressing to liver failure. The incidence and prevalence of the disease are increasing worldwide, possibly due to better diagnostic tools. This review will focus on its epidemiology, pathophysiology, diagnosis, prognosis, and new developments in therapy.

The impaired function of regulatory T (Treg) cells and the imbalance of Treg/Th17 cells play a central role in developing autoimmune diseases such as systemic lupus erythematosus (SLE). Treg cells are crucial for maintaining immune homeostasis and tolerance to self-antigens. One of the most important transcription factors that regulate the differentiation and function of Treg cells is the FOXP3 protein. Aberrant epigenetic modifications affecting FOXP3 gene expression and consequently dysregulated function of Treg cells have been implicated in the pathogenesis of SLE. Therefore, understanding the intricate interplay between FOXP3 expression pattern in Treg cells and epigenetic regulatory mechanisms (e.g., DNA methylation, histone modifications and non-coding RNAs such as microRNAs and long non-coding RNAs) is crucial for unravelling the underlying mechanisms of SLE. Moreover, targeting these epigenetic pathways may offer novel therapeutic strategies for restoring immune balance and ameliorating autoimmune pathology. This review report aimed to provide an update on the epigenetic controlling of FOXP3 gene expression in SLE disease.

Primary biliary cholangitis (PBC) is a chronic cholestatic progressive liver disease associated with cholangiopathies. The detection of antimitochondrial autoantibodies (AMAs) plays an important role in the diagnosis of classical PBC. AMAs are formed against the antigenic component associated with the dihydrolipoyl transacetylase of pyruvate dehydrogenase complex (E2 PDC) localized on the inner membrane of mitochondria. The loss of immune tolerance of E2 PDC in PBC is thought to be the cause of the mechanism of AMA formation and immune-mediated destruction of biliary epithelial cells (BECs) of the small- and medium-sized intrahepatic bile ducts. E2 PDC is not only present in BECs, but is also abundant in the mitochondria of all nucleated cells. The question remains as to why E2 PDC of only small BECs is the target of autoimmune attack. There is no evidence that AMAs have a deleterious effect on BECs. New scientific data has emerged that explains the damage to BECs in PBC by the defect of the biliary bicarbonate (HCO₃^–) “umbrella” that protects BECs from the detergent action of bile acids under physiological conditions. Disruption of HCO₃^– production by BECs in PBC leads to changes in the pH of hepatic bile, accompanied by accumulation of bile acids in the small BECs. The detergent action of bile acids leads to damage of membrane structures of BECs and their apoptosis, development of ductulopenia, and intrahepatic cholestasis. For the first time, it has been suggested that under the influence of bile acids, the E2 PDC antigen may undergo conformational changes that alter its immunological properties. E2 PDC becomes a neoantigen that is recognized by the normal (“healthy”) immune system as a foreign antigen, leading to the production of AMAs. For the first time, the authors of this review provide an explanation for why only small BECs are damaged in PBC.

Autoimmune diseases result from the immune system’s response to autoantigen components, leading to damage to one’s own tissues and organs. The correlation between long noncoding RNAs (lncRNAs) and autoimmune diseases remains inconclusive. However, recent studies have revealed that the lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) plays a vital role in the development of various autoimmune diseases. Here, this review briefly summarizes the progress in understanding NEAT1 expression variations and related mechanisms in different autoimmune diseases, and discusses its potential use for future therapeutic applications.

Complement is both evolutionary and scientifically old. It predates the adaptive immunity by some 600 million years and was first described in 1905 by Jules Bordet and Paul Ehrlich. For the most of its, the existence complement system has been ignored by most scientists and clinicians due to the perception of it being complicated and its relevance for the pathogenesis of human disease being unclear. With the recent US Food and Drug Administration (FDA) approvals of pegcetacoplan for both paroxysmal nocturnal haemoglobinuria (PNH) and geographic atrophy (GA), avacincaptad pegol for GA and iptacopan and danicopan for PNH, we are at a crucial juncture for complement-targeting therapies. A number of companies and academic institutions are developing next-generation complement therapies, which is resulting in an increasingly competitive landscape. If one looks at the serum complement cascade, all 3 pathways now have biotechnology or pharmaceutical industry players with 1 or multiple clinical-stage inhibitors that are expected to be FDA approved within the next few years. Furthermore, with the limited number of clinically validated targets in complement-mediated disease, the competition in this space is set to further intensify in the coming years. In this review, we will discuss the timeline of the academic discoveries that led to the development of the current crop of FDA-approved complement therapeutics. We follow with a discussion of an increasingly crowded complement therapy space and of the scientific advances that have emerged in recent two decades underpinning future innovation, including advances in our understanding of complement biology, such as local and intracellular complement, emerging complement targets, combinational approaches of complement and non-complement therapeutics to unlock new disease indications and new technologies such as gene therapy. We will also give a comprehensive overview of the gene therapy landscape and how it can be utilized to target complement dysregulation.

Type I diabetes susceptibility is caused by both environmental and genetic factors, the latter comprising approximately half of the total risk as evidenced by the fact that identical twins have approximately 50% concordance, suggesting 50% of the disease risk is environmental. The human leukocyte antigen (HLA) genes account for approximately half of the genetic risk, as demonstrated by the concordance between HLA identical siblings. Because environmental and genetic differences vary between racial groups, the incidence of type 1 diabetes (TID) differs across the world, being highest in Caucasians. Recent GWAS (genome-wide association studies) studies have suggested there may be up to 50 genomic regions contributing to the non-major histocompatibility complex (MHC) genetic risk contribution. This review presents and discusses the latest research on the MHC and non-MHC genes. Only the non-MHC regions, which have been confirmed in multiple studies and which are considered definite regions of genetic susceptibility, are included in the review.