The introduction of immune checkpoint inhibitors (ICIs) has transformed the landscape of oncology, offering significant improvements in patient survival and achieving remarkable long-term outcomes. Despite these advances, the therapeutic benefits of ICIs are not universal, and existing biomarkers often fall short in accurately predicting patient responses. A comprehensive understanding of the mechanisms underlying resistance to ICIs is essential for the development of strategies to mitigate these challenges and enhance therapeutic efficacy. This review provides a detailed exploration of the resistance mechanisms associated with ICIs, focusing on the role of the tumor microenvironment and intrinsic tumor cell alterations in mediating both primary and secondary resistance. Furthermore, it evaluates emerging strategies to overcome resistance, including combination therapies and innovative therapeutic approaches. By dissecting the molecular and immunological pathways implicated in ICI resistance, this review aims to highlight novel predictive and prognostic biomarkers and outline optimized therapeutic strategies to maximize the clinical impact of ICIs in cancer management.

Primary immunodeficiency disease (PID) now known as inborn errors of immunity (IEI) is genetic disorder(s) that impair the immune system. IEI is a heterogeneous group of diseases of more than 485 lifelong genetic disorders mainly due to intrinsic defect(s) in human immune system. Adults, children, and neonates can be affected by IEI diseases. The first IEI defects were reported in the 1950s, but Bruton’s use of immunoglobulin in 1952 to treat an 8-year-old boy suffering from pneumonia and other bacterial sino-pulmonary infections brought the PID or IEI and associated diseases into limelight. This review will focus on a general description of IEI (history, epidemiology, pathophysiology, and diagnosis), inborn errors of metabolism, and the management (cure or therapy) of IEI diseases.

Monogenic muscular dystrophies (MDs), such as Duchenne muscular dystrophy (DMD) and limb-girdle muscular dystrophy (LGMD), are characterized by chronic inflammation, progressive fibrosis, and impaired muscle regeneration. Central to these pathological processes are macrophages, which exhibit dynamic polarization states that influence the dystrophic microenvironment. In early disease stages, macrophages support tissue repair and regeneration, but chronic inflammation skews their activity toward pro-fibrotic phenotypes, driving excessive extracellular matrix (ECM) deposition and muscle dysfunction. Macrophages also interact with other immune cells, such as T cells and neutrophils, and non-immune cells, including fibroblasts and satellite cells, to regulate inflammatory and fibrotic responses. These interactions establish a dysregulated immune environment that exacerbates muscle damage and impairs effective regeneration. Preclinical studies using the mdx mouse model of DMD highlight the critical role of macrophages in sustaining inflammation and fibrosis, particularly through transforming growth factor-beta (TGF-β) signaling and fibro-adipogenic progenitor (FAP) activation. Therapeutically, targeting macrophages offers significant potential to mitigate disease progression. Strategies include modulating macrophage polarization toward a pro-regenerative M2 phenotype, inhibiting macrophage recruitment via chemokine signaling, and reprogramming macrophage metabolism to support oxidative phosphorylation and mitochondrial function. Additionally, anti-fibrotic interventions targeting TGF-β signaling or macrophage-FAP crosstalk have shown promise in reducing ECM deposition and preserving muscle architecture. In this review, we curate relevant studies and provide insights into the molecular mechanisms governing macrophage behavior in dystrophic muscle. Herein, we discuss how emerging therapeutic strategies targeting macrophage-mediated pathways can be leveraged to mitigate inflammation and fibrosis, enhance muscle regeneration, and improve clinical outcomes.

Diet plays a complex role in the management of inflammatory bowel disease (IBD), significantly influencing the microbiome and metabolome. Three key metabolites implicated in IBD are short chain fatty acids, bile acids and tryptophan, all of which can be modulated through diet. This study analyses the impact of various diets on these metabolites. Despite the anti-inflammatory effects of short chain fatty acids, their levels do not increase during successful remission with exclusive enteral nutrition. Additionally, changes in tryptophan and bile acids are non-specific across different diets, suggesting these metabolic shifts are secondary to dietary efficacy in IBD. Dietary therapies vary in efficacy across individuals, as the established microbiome may not produce the desired metabolites. This variability is further compounded by differences in immune responses influenced by genetic factors and disease duration. Furthermore, inflammation and symptom resolution do not always coincide, revealing a discrepancy in dietary impacts on IBD. These limitations highlight the need for a deeper understanding of the interconnectedness of disease heterogeneity, dietary effects, the microbiome, and their influence on the mucosal immune system to develop more personalised dietary therapies. While no single diet is universally effective for all IBD patients, future research should focus on establishing a more rigid definition of dietary interventions for IBD and their long-term effects on clinical outcomes.

Neoantigen vaccines are a promising strategy in cancer immunotherapy that leverage tumor-specific mutations to elicit targeted immune responses. Although they have considerable potential, development challenges related to antigen prediction accuracy, manufacturing complexity, and scalability remain key obstacles to their widespread clinical use. This literature review was conducted using PubMed, Scopus, Web of Science, and Google Scholar databases to identify relevant studies. Keywords included “neoantigen vaccines,” “personalized cancer immunotherapy,” “tumor heterogeneity,” “bioinformatics pipelines,” and “prediction algorithms”. Clinical trial data were sourced from ClinicalTrials.gov, Trialtrove, and other publicly available registries. Eligible studies included peer-reviewed research articles, systematic reviews, and clinical trials focusing on neoantigen vaccine development, bioinformatic strategies, and immunotherapy. Tumor heterogeneity and clonal evolution significantly impact vaccine efficacy, necessitating multi-epitope targeting and adaptive vaccine design. Current neoantigen prediction algorithms suffer from high false-positive and false-negative rates, requiring further integration with multi-omics data and machine learning to enhance accuracy. Manufacturing remains complex, time-intensive, and costly, necessitating advancements in standardization and automation. Combination therapies, such as immune checkpoint inhibitors and adoptive cell therapies, counteract the immunosuppressive tumor microenvironment, improving treatment outcomes. Neoantigen vaccines hold great potential for personalized cancer therapy but require advancements in bioinformatics, manufacturing scalability, and immunomodulatory strategies to enhance clinical efficacy. Continued research and interdisciplinary collaboration are essential for refining clinical applications.

Cutaneous reactions present a diagnostic challenge, mainly when multiple factors, such as infections, medications, and environmental triggers, contribute to the clinical picture. Erythema multiforme (EM) is an acute, self-limiting mucocutaneous disorder that is most commonly triggered by herpes simplex virus (HSV) but can also be associated with drug-induced hypersensitivity reactions. Diagnosing EM becomes even more complex in patients taking photosensitizing medications, such as doxycycline, which can cause phototoxic or photoallergic reactions. Differentiating between drug-induced and infection-associated EM, as well as distinguishing it from more severe conditions like Stevens-Johnson syndrome (SJS), is crucial for appropriate management. This case report presents a case of a 57-year-old Caucasian female with a history of penicillin allergy who developed a phototoxic reaction to doxycycline following sun exposure. She was treated with silver sulfadiazine for her skin lesions but subsequently developed EM, with target-like lesions predominantly on the legs and a concurrent herpes simplex labialis infection. Laboratory findings were unremarkable, and there was no mucosal involvement. Given the suspected drug-induced nature of the reaction and the presence of HSV, a cautious approach was taken. Treatment with oral prednisone led to the resolution of symptoms without recurrence. Patch testing for doxycycline and silver sulfadiazine was omitted due to the risk of severe cutaneous adverse drug reactions (SCARs) and their non-essential status. Instead, penicillin testing was prioritized due to its clinical importance, and the patient successfully passed the oral amoxicillin challenge. This case highlights the diagnostic challenges of differentiating between drug-induced, infection-triggered, and photosensitivity-related cutaneous reactions. A careful evaluation of medication history, infection status, and clinical presentation is essential to guide the management of this condition.

Immune response, inflammation, and lipid metabolism have important effects on cancer development and progression. Several proteins in tumoral cells and/or tumor microenvironment are involved in any of these processes, whereas some of them participate in all three, such as the zinc finger E-box-binding homeobox 1 (ZEB1) protein. This protein has been proposed to have an important role in invasion and metastasis of cancer cells, as well as to be involved in malignant transformation and resistance to cancer treatments. So, in this study, we present the participation of ZEB1 in immune, inflammatory, and membrane remodeling (lipid metabolism) processes, as well as its interaction with proteins that participate in them. Due to the importance of ZEB1 in cancer progression, it may be a potential biomarker of cancer prognosis and a target for the development of new cancer therapies.

In hematological malignancies, autologous immunotherapy with T lymphocytes expressing a chimeric antigen receptor (CAR-T) has been successfully applied. CAR enhances the immuno-cellular effector system directly against cells expressing target antigens. The objective here was to discuss the prospects of applying CAR-T and its variants in autoimmune diseases (AIDs) to deplete pathogenic autoantibodies by eliminating B lymphocytes and plasma cells. B cells play a crucial role in the pathogenesis of AID through the production of autoantibodies, cytokine dysregulation, antigen presentation, and regulatory dysfunction. In AID with numerous autoreactive clones against various autoantigens, such as systemic lupus erythematosus, rheumatoid arthritis, vasculitis, myositis, and systemic sclerosis, CAR-T targeting CD19/CD20 and B-cell maturation antigen (BCMA) have shown success in preclinical and clinical studies, representing an innovative option for refractory patients when standard treatments fail. The suppression of B lymphocytes reactive against specific antigens using cytolytic T cells carrying a chimeric autoantibody receptor (CAAR-T) offers a promising approach for managing various AIDs, especially those with characterized pathogenic autoantibodies, such as pemphigus vulgaris, myasthenia gravis, and anti-NMDAR autoimmune encephalitis. CAAR-T allows the elimination of autoreactive B lymphocytes without compromising the general functionality of the immune system, minimizing common side effects in general immunosuppressive therapies, including immunobiologicals and CAR-T. In vitro, preclinical, and clinical (phase 1) studies have demonstrated the efficacy and specificity of CAR-T and CAAR-T in several AIDs; however, extensive clinical trials (phase 3) are required to assess their safety and clinical applicability. These advances promise to enhance precision medicine in the management of AIDs, offering personalized treatments for individual patients.

Wound healing is an area of growing importance in the healthcare field, especially chronic wounds associated with comorbidities like diabetes mellitus (DM), hypoxic stress, obesity, and malnutrition. Chronic wounds significantly increase healthcare costs and reduce patients’ quality of life. Cytokines are a promising therapeutic target, as they regulate all stages of wound healing, and dysfunction in cytokine production can cause inflammatory non-healing wounds. Interleukin-1 (IL-1), IL-2, IL-6, IL-8, and tumour necrosis factor-α (TNF-α) facilitate leukocyte recruitment and clear dead cells during the initial inflammation stage while transforming growth factor-β (TGF-β), IL-4, and IL-13 inhibit inflammation and stimulate proliferation of fibroblasts to begin extracellular matrix (ECM) deposition. Given the complexity of cytokine interactions and their diverse cellular targets, a comprehensive understanding of these signaling pathways is crucial. This review examines the multifaceted roles of cytokines in wound healing and discusses recent advancements in the therapeutic application of cytokine modulation for improved wound care outcomes. Despite significant advancements in improving the specificity of cytokine therapies, further research is needed to focus on targeting downstream signaling pathways or specific receptors to minimize the adverse effects associated with these treatments.

Coronavirus disease 2019 (COVID-19) infected individuals showed either mild symptoms or were paucisymptomatic, with severe impact on human health, revealing heightened risk and direct effects on health. Among various factors contributing to complications, bacterial and fungal co-infection remains very common and is highly lethal. This narrative review aims to focus on the collective role of gut microbiota and mycobiota in COVID-19. Fungal infection has been identified as a key risk factor for the spread of COVID-19 and mortality. Gut mycobiomes diversity and abundance also vary due to the different types of SARS-CoV-2 variant infection. Their cross-talk plays a vital role in immune regulation and disease severity, with an emphasis on understanding the altered condition as a predictive marker. On the other hand, the gut microbiome is well known for shaping metabolic functions, generating immune responses, and deciphering the signal to decide the healthy state and disease condition of an individual. Immune response during COVID-19 infection was also linked with metabolites produced by the gut microflora, specifically amino acids, sugar metabolites, and neurotransmitters. The cross-talk between gut microbiota and gut mycobiota for clinical implications in terms of early detection, identification of the disease severity, and even therapeutic alternatives will open newer avenues. A deep dive understanding of the cross-talk between the microbiome and mycobiome, and their role in immune response will take scientific discovery knowledge to develop gut-targeted safe therapeutic approaches in the form of FMT (fecal microbiota transplantation) probiotics, peptides, antibacterial, and antifungal metabolites. Overall cross-talk and immune interplay are critical determinants of host immunity, providing insights into their role and key take home lessons for better management of crisis in the future.

Nociplastic pain is the fourth category of pain defined in recent years. It is a pain arising from altered nociception, despite the lack of clear evidence of actual or threatened tissue damage that causes activation of peripheral nociceptors nor evidence for disease or lesion of the somatosensory system causing the pain. This type of pain is usually multifocal, more diffuse or intense than expected and it is usually associated with other central nervous system-derived symptoms, such as fatigue, sleep, memory, and mood problems. It can occur in isolation or as part of a mixed-pain state in combination with ongoing nociceptive or neuropathic pain. It is associated with increased social and sanitary costs due to the difficulty of adequately treating it. Its pathogenesis is still poorly understood, even if a mounting body of evidence suggests a pivotal role in inflammation and immunity, which may be triggered by an infection and/or a trauma. This narrative review aims to summarise the current knowledge about the interplay of the immune system and nociplastic pathways activation and amplification. The challenge for the future will be to identify the exact role of inflammation and immunity, the cause of this activation, and its link to other pathogenetic factors of nociplastic pain, such as diet or microbiota alteration, social and phycological factors, together with a genetic and epigenetic predisposition.

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.