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Immunotherapy for Hepatocellular Carcinoma: Current Status and Future Prospects.

Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer with poor prognosis. Surgery, chemotherapy, and radiofrequency ablation are three conventional therapeutic options that will help only a limited percentage of HCC patients. Cancer immunotherapy has achieved dramatic advances in recent years and provides new opportunities to treat HCC. However, HCC has various etiologies and can evade the immune system through multiple mechanisms. With the rapid development of genetic engineering and synthetic biology, a variety of novel immunotherapies have been employed to treat advance

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… ICIs can cause inflammatory side effects, including hypophysitis, thyroid dysfunction, and diabetes. CAR-T therapy can cause some severe side effects such as cytokine release syndrome (CRS), neurotoxicity, and even death. …

Common Non-Rheumatic Medical Conditions Mimicking Fibromyalgia: A Simple Framework for Differential Diagnosis.

Fibromyalgia (FM) is a chronic non-inflammatory disorder mainly characterized by widespread musculoskeletal pain, fatigue, sleep disturbances, and a constellation of other symptoms. For this reason, delineating a clear distinction between pure FM and FM-like picture attributable to other common diseases can be extremely challenging. Physicians must identify the most significant confounders in individual patients and implement an appropriate diagnostic workflow, carefully choosing a minimal (but sufficient) set of tests to be used for identifying the most plausible diseases in the specific case

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… Most cases of central hypothyroidism are due to a compressive lesion of the pituitary sella, such as pituitary adenomas or meningiomas, cranial surgery or radiation therapy, autoimmune disease (hypophysitis) [ 56 ] or drugs such as glucocorticoids [ 54 ]. …

Clinical Insights Into Novel Immune Checkpoint Inhibitors.

The success of immune checkpoint inhibitors (ICIs), notably anti-cytotoxic T lymphocyte associated antigen-4 (CTLA-4) as well as inhibitors of CTLA-4, programmed death 1 (PD-1), and programmed death ligand-1 (PD-L1), has revolutionized treatment options for solid tumors. However, the lack of response to treatment, in terms of de novo or acquired resistance, and immune related adverse events (IRAE) remain as hurdles. One mechanisms to overcome the limitations of ICIs is to target other immune checkpoints associated with tumor microenvironment. Immune checkpoints such as lymphocyte activation ge

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… Both treatment arms had tolerable safety profiles, with the combination treatment showing one grade 34 immune-related hypophysitis. Further assessments of the pharmacokinetic (PK) and pharmacodynamic (PD) markers and the anti-tumor activity of the monotherapy and combination are awaiting results. …

The role of tumor types in immune-related adverse events.

Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that block inhibitors of T cell activation and function. With the widespread use of ICIs in cancer therapy, immune-related adverse events (irAEs) have gradually emerged as urgent clinical issues. Tumors not only exhibit high heterogeneity, and their response to ICIs varies, with "hot" tumors showing better anti-tumor effects but also a higher susceptibility to irAEs. The manifestation of irAEs displays a tumor-heterogeneous pattern, correlating with the tumor type in terms of the affected organs, incidence, median onset time, and se

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… For example, ICIs can target the hypothalamic and pituitary tissues expressing CTLA-4, leading to hypophysitis [ 53 ]. …

Physiological Role and Use of Thyroid Hormone Metabolites - Potential Utility in COVID-19 Patients.

Thyroxine and triiodothyronine (T3) are classical thyroid hormones and with relatively well-understood actions. In contrast, the physiological role of thyroid hormone metabolites, also circulating in the blood, is less well characterized. These molecules, namely, reverse triiodothyronine, 3,5-diiodothyronine, 3-iodothyronamine, tetraiodoacetic acid and triiodoacetic acid, mediate both agonistic (thyromimetic) and antagonistic actions additional to the effects of the classical thyroid hormones. Here, we provide an overview of the main factors influencing thyroid hormone action, and then go on t

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… In summary, NTIS, elevated IL-6 and TNF-α levels, glucocorticoid treatment and hypophysitis may cause a similar pattern of decreased TSH levels, slightly reduced T4 and T3 levels. SAT and atypical thyroiditis, by contrast, would be characterized by transiently elevated T4 and T3 levels. …

Bone health in patients with cancer: a SEOM-SEIOMM consensus review of risk factors, assessment strategies, and management approaches.

Anticancer therapies frequently compromise skeletal health and increase fracture risk. This narrative review synthesizes information and provides guidance on assessment, prevention, and management of therapy-related bone loss in adults with cancer. Major contributors to bone loss in this population include aromatase inhibitors, androgen deprivation therapy, systemic glucocorticoids, chemotherapy, and selected targeted or immune agents. Recommended assessments include clinical evaluation, laboratory tests (calcium, vitamin D, and renal function), and bone mineral density by dual-energy X-ray ab

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… ICIs can lead to endocrinopathies such as hypophysitis, resulting in adrenal insufficiency and hypothyroidism and sometimes to hypogonadotropic hypogonadism requiring hormone replacement [ 105 ]. These endocrine disruptions can contribute to bone loss [ 106 ]. …

Cancer Resistance to Immunotherapy: Comprehensive Insights with Future Perspectives.

Cancer immunotherapy is a type of treatment that harnesses the power of the immune systems of patients to target cancer cells with better precision compared to traditional chemotherapy. Several lines of treatment have been approved by the US Food and Drug Administration (FDA) and have led to remarkable success in the treatment of solid tumors, such as melanoma and small-cell lung cancer. These immunotherapies include checkpoint inhibitors, cytokines, and vaccines, while the chimeric antigen receptor (CAR) T-cell treatment has shown better responses in hematological malignancies. Despite these

Systemic Sclerosis Association with Malignancy.

The association of systemic sclerosis (SSc) and cancer is well known from several decades suggesting common genetic and environmental risk factors involved in the development of both diseases. Immunosuppressive drugs widely used in SSc may increase the risk of cancer occurrence and different SSc clinical and serological features identify patients at major risk to develop malignancy. In this context, among serological features, presence of anti-RNA polymerase III and anti-topoisomerase I autoantibodies seems to increase cancer frequency in SSc patients (particularly lung and breast cancers). Lu

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… The most common endocrine disorders include CTLA-4 blocking hypophysitis and anti-PD-1-induced hypothyroidism, affecting approximately 10% of patients. …

The Use of Immune Checkpoint Inhibitors in Oncology and the Occurrence of AKI: Where Do We Stand?

Immune checkpoint inhibitors (ICIs) are a novel class of immunotherapy drugs that have improved the treatment of a broad spectrum of cancers as metastatic melanoma, non-small lung cancer or renal cell carcinoma. These humanized monoclonal antibodies target inhibitory receptors (e.g. CTLA-4, PD-1, LAG-3, TIM-3) and ligands (PD-L1) expressed on T lymphocytes, antigen presenting cells and tumor cells and elicit an anti-tumor response by stimulating immune system. Nevertheless, the improved overall survival is complicated by the manifestation of Immune-related Adverse Effects (irAEs). During treat

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… Thus, the most frequent ICIs-induced irAEs are dermatitis, rash, vitiligo, colitis, pneumonitis, hypophysitis, hypothyrodims, and other endocrinopathies ( 35 ). The incidence of irAEs is wide, ranging from 15% to 90%, with severe forms ranging from 0.5% to 13% ( 36 ). …

Comprehensive view on chemotherapy-free management of acute myeloid leukemia by using venetoclax in combination with targeted and/or immune therapies.

A hallmark of cancer biology is resistance to apoptosis. BCL-2 is an anti-apoptotic molecule that is being overexpressed in several myeloid diseases, such as acute myeloid leukemia and myelodysplastic syndromes, but also in several lymphoid cancers, such as acute lymphoblastic leukemia, chronic lymphocytic leukemia, non-Hodgkin lymphomas and multiple myeloma. Venetoclax (VEN) is a BCL-2 small molecule inhibitor. Data about its structure, biochemical characteristics and in vitro efficacy against several blood cancer cell lines were first reported in 2013. Shortly after, the first clinical trial

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… Up to 30% of patients may also present with endocrine system involvement, including thyroiditis, hypophysitis, and type 1 diabetes [ 111 ]. Combining checkpoint-inhibitors with other chemotherapy agents increased the risk of hypotension, myocarditis and arrhythmias [ 112 ]. …

Innovations in cancer treatment as novel potential and the myth of personalized vaccines, immunotherapy, CRISPR/Cas9, and bacteriotherapy as promising therapeutic strategies.

Recent advancements in cancer treatment, including targeted therapy, tailored vaccines, immunotherapy, and bacteriotherapy, have demonstrated remarkable potential in addressing various types of cancer. However, the pursuit of novel therapeutic strategies remains challenged by significant obstacles, including toxicity to healthy tissues, limited penetration into malignant tissues, and the potential for tumor cell resistance to pharmacological agents. This study explored the potential of tailored vaccinations, immunotherapy, CRISPR/Cas9, and bacteriotherapy for cancer treatment. Randomized and n

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… The most widespread of them are skin reactions (including rash and itching), gastrointestinal (including diarrhoea and colitis), and endocrine (including thyroid disorders, hypophysitis, and adrenal insufficiency) conditions. …

Pharmacovigilance in Cell and Gene Therapy: Evolving Challenges in Risk Management and Long-Term Follow-Up.

Cell and gene therapies, including CAR T-cells, CRISPR-based genome editing, and next-generation viral and non-viral delivery platforms, are transforming treatment paradigms across cancer, rare genetic disorders, immune dysregulation, and neurodegenerative disease. These therapies offer curative potential but also present safety challenges owing to prolonged biological activity, systemic immune engagement, and lasting genomic alterations. This review examines the range of related toxicities, including immune complications, genotoxicity, and organ-specific effects, with attention to atypical pr

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… Endocrine complications, including thyroiditis, primary adrenal insufficiency, and hypophysitis, occur in approximately 5–10% of CAR T-cell therapy recipients and often emerge months after treatment [ 103 ]. …

Emerging therapeutics in the management of COVID-19.

The severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019, COVID-19) pandemic has placed a tremendous burden on healthcare systems globally. Therapeutics for treatment of the virus are extremely inconsistent due to the lack of time evaluating drug efficacy in clinical trials. Currently, there is a deficiency of published literature that comprehensively discusses all therapeutics being considered for the treatment of COVID-19. A review of the literature was performed for articles related to therapeutics and clinical trials in the context of the current COVID-19 pandemic. We

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… Previously reported adverse effects vary including the following disturbances: gastrointestinal (bloody diarrhea, abdominal pain, and pyrexia), hepatic (jaundice, and asymptomatic liver enzyme elevation), endocrine (hypophysitis, hypo/hyperthyroiditis, primary adrenal insufficiency, and hypercalcemia …

A guide to cancer immunotherapy: from T cell basic science to clinical practice.

The T lymphocyte, especially its capacity for antigen-directed cytotoxicity, has become a central focus for engaging the immune system in the fight against cancer. Basic science discoveries elucidating the molecular and cellular biology of the T cell have led to new strategies in this fight, including checkpoint blockade, adoptive cellular therapy and cancer vaccinology. This area of immunological research has been highly active for the past 50 years and is now enjoying unprecedented bench-to-bedside clinical success. Here, we provide a comprehensive historical and biological perspective regar

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… Ipilimumab (anti-CTLA4 antibody) causes regression of metastatic renal cell cancer associated with enteritis and hypophysitis. J. Immunother. 2007;30:825–830. doi: 10.1097/CJI.0b013e318156e47e. 59. Lynch TJ, et al. …

Advances in the understanding and therapeutic manipulation of cancer immune responsiveness: a Society for Immunotherapy of Cancer (SITC) review.

Cancer immunotherapy-including immune checkpoint inhibition (ICI) and adoptive cell therapy (ACT)-has become a standard, potentially curative treatment for a subset of advanced solid and liquid tumors. However, most patients with cancer do not benefit from the rapidly evolving improvements in the understanding of principal mechanisms determining cancer immune responsiveness (CIR); including patient-specific genetically determined and acquired factors, as well as intrinsic cancer cell biology. Though CIR is multifactorial, fundamental concepts are emerging that should be considered for the desi

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… adverse events (irAEs). 24 In the registrational randomized trials of these agents, Grade 3 or 4 irAEs occur in~20% of anti-CTLA-4 treated patients, 25 ~12% with anti-PD-1, and~50% with CTLA-4/PD-1 combinations. 26 irAEs can involve any organ system and include dermatitis, colitis, hypothyroidism, hypophysitis …

Advances and clinical applications of immune checkpoint inhibitors in hematological malignancies.

Immune checkpoints are differentially expressed on various immune cells to regulate immune responses in tumor microenvironment. Tumor cells can activate the immune checkpoint pathway to establish an immunosuppressive tumor microenvironment and inhibit the anti-tumor immune response, which may lead to tumor progression by evading immune surveillance. Interrupting co-inhibitory signaling pathways with immune checkpoint inhibitors (ICIs) could reinvigorate the anti-tumor immune response and promote immune-mediated eradication of tumor cells. As a milestone in tumor treatment, ICIs have been first

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… Hypophysitis was associated with anti‐CTLA‐4 therapy [ 69 ], while thyroid dysfunction was associated with anti‐PD‐1 therapy [ 168 ]. Diabetes and adrenal insufficiency are comparatively rare but can be fatal if left untreated [ 167 ]. …

Cardio-oncology in Austria: cardiotoxicity and surveillance of anti-cancer therapies : Position paper of the Heart Failure Working Group of the Austrian Society of Cardiology.

Survival in cancer is continuously improving due to evolving oncological treatment. Therefore, cardiovascular short-term and long-term side effects gain crucial importance for overall outcome. Cardiotoxicity not only presents as heart failure, but also as treatment-resistant hypertension, acute coronary ischemia with plaque rupture or vasospasm, thromboembolism, arrhythmia, pulmonary hypertension, diastolic dysfunction, acute myocarditis and others. Recent recommendations have proposed baseline cardiac risk assessment and surveillance strategies. Major challenges are the availability of monito

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… and China) with presently over 50 indications and rapidly expanding, e.g. gastric, colorectal, renal cell, laryngeal, breast cancer and urogenital; however, the augmented immune response has led to a range of immune-related adverse events (irAE), e.g. interstitial pneumonia, colitis, hypothyroidism, hypophysitis …

RESEARCH COMMUNICATIONS OF THE 28th ECVIM-CA CONGRESS.

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Revitalizing T cells: breakthroughs and challenges in overcoming T cell exhaustion.

T cell exhaustion is a prevalent phenomenon in chronic infections and tumor microenvironments, severely compromising the effectiveness of antitumor and antiviral immunity. In recent years, there has been significant progress in understanding the underlying mechanisms of T cell exhaustion, including external factors and intrinsic cellular changes that drive this dysfunctional state. Key external factors such as persistent antigen exposure, immune checkpoint signaling, and the cytokine milieu, as well as intrinsic changes such as altered metabolic processes, epigenetic modifications, and transcr

One step further in targeting acute leukemia by combining antibody-based immunotherapies and small molecule inhibitors.

BackgroundAcute leukemia is a bone marrow-related disease characterized by fast progression and the production of immature blood cells rather than normal ones that are classified as either acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML). Chemotherapy as a conventional treatment has many side effects, thus new medications that target intracellular molecules and cell surface markers on leukemic cells have been developed in the last decades.Main bodyThis review focuses on antibody-based targeted treatments, which so far, have been shown to improve the treatment outcomes, includ

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… individuals receiving ICIs for advanced cancers have a higher chance of experiencing immune-related neurological side effects, such as myasthenia gravis, inflammatory myopathies, acute and chronic demyelinating polyradiculoneuropathies, vasculitic neuropathies, and isolated cranial neuropathies, and hypophysitis …