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Induced proximity strategies for modulating immune checkpoints in cancer immunotherapy.

Immune checkpoints (ICs) serve as critical negative regulators of immune responses, which maintain tolerance and limit inflammation. Tumor cells evade immune surveillance by upregulating ICs and accumulating immunosuppressive molecules in the tumor microenvironment. Immune checkpoint inhibitors, especially monoclonal antibody-based immune checkpoint blockade therapy, demonstrate durable clinical efficacy but face limitations: immune-related adverse events (irAEs), acquired resistance, and limited patient response. Induced proximity strategies, exemplified by proteolysis-targeting chimeras (PRO

Targeting the NF-κB pathway as a potential regulator of immune checkpoints in cancer immunotherapy.

Advances in cancer immunotherapy over the last decade have led to the development of several agents that affect immune checkpoints. Inhibitory receptors expressed on T cells that negatively regulate the immune response include cytotoxic T‑lymphocyte antigen 4 (CTLA4) and programmed cell death protein 1 (PD1), which have been studied more than similar receptors. Inhibition of these proteins and other immune checkpoints can stimulate the immune system to attack cancer cells, and prevent the tumor from escaping the immune response. However, the administration of anti-PD1 and anti-CTLA4 antibodies

[Cutaneous Toxicity of Immune Checkpoint Inhibitors: A Narrative Review].

INTRODUCTION: Immune checkpoint inhibitors revolutionized anti-neoplastic treatment. Recently, the European Medicines Agency and the United States Food and Drug Administration approved inhibitors of various immune checkpoints, namely the cytotoxic T-lymphocyte-associated protein 4, programmed cell death protein 1 and its ligand. Despite the added benefits in the treatment of several neoplasms, immune checkpoint blockade may also be associated with multiple immune-related adverse events. MATERIAL AND METHODS: A literature review in PubMed database on the cutaneous toxicity of immune checkpoint

Use of Immune Checkpoint Inhibitors in Solid-Organ Transplant Patients: An Orphan Issue.

Immune checkpoint inhibitors block inhibitory signals on T cells, enabling the immune system to fight cancer cells more effectively. Immune checkpoints such as programmed cell death protein 1/programmed cell death ligand 1 and cytotoxic T-lymphocyte-associated protein 4 normally limit the immune response, preventing excessive immune reactions. However, cancer cells can evade the immune system by using these signals. Immune checkpoint inhibitors restore T-cell activity by blocking these escape mechanisms and by directing them to destroy cancer cells. Patients undergoing solid-organ transplant m

Agonistic and antagonistic targeting of immune checkpoint molecules differentially regulate osteoclastogenesis.

INTRODUCTION: Immune checkpoint inhibitors are used in the treatment of various cancers and have been extensively researched with regard to inflammatory and autoimmune diseases. However, this revolutionary therapeutic strategy often provokes critical auto-inflammatory adverse events, such as inflammatory reactions affecting the cardiovascular, gastrointestinal, nervous, and skeletal systems. Because the function of these immunomodulatory co-receptors is highly cell-type specific and the role of macrophages as osteoclast precursors is widely published, we aimed to analyze the effect of immune c

Immune Checkpoints: Therapeutic Targets for Pituitary Tumors.

Pituitary tumors are the third most common intracranial tumors in adults. Treatment of refractory pituitary tumors is known to be difficult due to limited treatment options. As a promising therapeutic method, tumor immunotherapy has been applied in the treatment of many tumors, including pituitary tumors. Immune checkpoint blocking is one of the effective strategies to activate antitumor immunity. Immune checkpoints prevent tissue damage by regulating the immune response of peripheral tissues and participate in the maintenance of a normal immune environment. In the presence of a tumor, inhibit

Novel insights into immune checkpoints in psoriasis and atopic dermatitis: From expression and function to treatments.

Psoriasis and atopic dermatitis (AD) are both chronic inflammatory skin diseases, which are common and difficult to cure. Currently, the emerging biologics have demonstrated outstanding efficacy, but not all patients are able to benefit from them, and traditional systemic treatments come with many severe side effects. The emergence of immune checkpoints brings new hope to solve this problem. Immune checkpoints regulate T cell activation. Upon damage to the co-inhibitory molecules, the inhibition on T cells is removed, leading to the excessive activation of T cells. In this review, we delineate

The ubiquitin-proteasome system in the tumor immune microenvironment: a key force in combination therapy.

The ubiquitin-proteasome system (UPS) plays a crucial role in modulating the proliferation, activation, and normal functioning of immune cells through the regulation of protein degradation and function. By influencing the expression of immune checkpoint-associated proteins, the UPS modulates T cell-mediated anti-tumor immune responses and can potentially facilitate the immune escape of tumor cells. Additionally, the UPS contributes to the remodeling of the tumor immunosuppressive microenvironment (TIME) by regulating B cells, dendritic cells (DCs), macrophages, and Treg cells. Targeting the UP

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… The high expression of tumor immune checkpoint proteins inhibits immune recognition and normal immune responses ( 8 ). … These E3 ligases affect the stability, localization, and function of immune checkpoint proteins through specific ubiquitination events ( 42 ). …

Prostate Cancer Therapy via Inhibition of Negative Immune Regulation.

Prostate cancer exhibits complex pathophysiology, rendering its management arduous due to heterogeneity and recalcitrance toward conventional therapeutics. The increasing focus on immune checkpoint inhibitors for treatment stems from the limited existing therapeutic approaches and the impressive effectiveness of these inhibitors demonstrated in other malignancies. Denoted as immunologically "cold" with low tumor mutation burden (TMB), prostate cancer manifests diminished immune cell infiltration in tumoral tissue, potentially culminating in inadequate response to immune checkpoint blockade. No

Inhibitory immune checkpoints in preeclampsia: current landscape, mechanisms, and clinical perspectives.

Preeclampsia (PE) is a pregnancy-specific disorder whose pathogenesis remains incompletely elucidated. The prevailing theory suggests that compromised maternal-fetal immune tolerance is a key contributor. In recent years, inhibitory immune checkpoints have garnered considerable attention as key regulatory factors in maintaining immune homeostasis during pregnancy. Programmed cell death protein 1 (PD-1), T cell immunoglobulin and mucin domain-containing protein 3 (Tim-3), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), T cell immunoreceptor with Ig and ITIM domains (TIGIT), and lymphocyte

Immune Checkpoint Blockade in Hematological Malignancies: Current Status and Future Directions.

Immune checkpoint proteins including PD-1, CTLA-4, LAG-3, TIM-3, and TIGIT regulate T-cell functions, which are essential for anti-tumor immunity. Over-expression of these immune checkpoint proteins leads to T-cell exhaustion and a significant impairment of anti-tumor immunity. Rejuvenation of effector T-cell function with immune checkpoint inhibitors (ICI) restores anti-tumor immunity, which translates into clinical efficacy in the frontline and salvage treatment of various hematological malignancies. Efficacy of ICIs is highest in classical Hodgkin lymphoma, primary mediastinal large B-cell …

Icaritin-induced immunomodulatory efficacy in advanced hepatitis B virus-related hepatocellular carcinoma: Immunodynamic biomarkers and overall survival.

Advanced hepatitis B virus (HBV)-related hepatocellular carcinoma HCC with poor prognosis is often associated with chronic inflammation, imm … n of MDSCs was evaluated in BALB/c mice in vivo. Immunomodulation of serum cytokines and a panel of immune checkpoint proteins were assessed in HBV-related, histologically confirmed HCC patients. Poor prognostic characteristics included HBV infection, bulky tumors, Child-Pugh B classification, and metastasis. Clinical end-points included safety, tumor response, and overall …

Immune checkpoints in cardiac physiology and pathology: therapeutic targets for heart failure.

Immune checkpoint molecules are physiological regulators of the adaptive immune response. Immune checkpoint inhibitors (ICIs), such as monoclonal antibodies targeting programmed cell death protein 1 or cytotoxic T lymphocyte-associated protein 4, have revolutionized cancer treatment and their clinical use is increasing. However, ICIs can cause various immune-related adverse events, including acute and chronic cardiotoxicity. Of these cardiovascular complications, ICI-induced acute fulminant myocarditis is the most studied, although emerging clinical and preclinical data are uncovering the impo

Immune checkpoint inhibitors and cancer immunotherapy by aptamers: an overview.

Efforts in cancer immunotherapy aim to counteract evasion mechanisms and stimulate the immune system to recognise and attack cancer cells effectively. Combination therapies that target multiple aspects of immune evasion are being investigated to enhance the overall efficacy of cancer immunotherapy. PD-1 (Programmed Cell Death Protein 1), CTLA-4 (Cytotoxic T-Lymphocyte Antigen 4), LAG-3 (Lymphocyte-Activation Gene 3), and TIM-3 (T Cell Immunoglobulin and Mucin Domain-Containing Protein3) are all immune checkpoint receptors that play crucial roles in regulating the immune response and maintainin

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

Совпадение в полном тексте источника
… The expression of immune checkpoint proteins by tumor cells dysregulates the anti‐tumor immunity, suppresses the immune function of T cells, and favors the growth and expansion of cancer tumor cells. …

Review of T Helper 2-Type Inflammatory Diseases Following Immune Checkpoint Inhibitor Treatment.

Immune checkpoints are mechanisms that allow cancer cells to evade immune surveillance and avoid destruction by the body's immune system. Tumor cells exploit immune checkpoint proteins to inhibit T cell activation, thus enhancing their resistance to immune attacks. Immune checkpoint inhibitors, like nivolumab, work by reactivating these suppressed T cells to target cancer cells. However, this reactivation can disrupt immune balance and cause immune-related adverse events. This report presents a rare case of prurigo nodularis that developed six months after administering nivolumab for lung aden…

Development of small molecule drugs targeting immune checkpoints.

Immune checkpoint inhibitors (ICIs) are used to relieve and refuel anti-tumor immunity by blocking the interaction, transcription, and trans … is review we summarized the current progression of small molecule ICIs and the mechanism underlying immune checkpoint proteins, which will lay the foundation for further exploration.

Anti-CTLA-4 therapy-associated granuloma annulare in chronic myelomonocytic leukemia.

Immune checkpoint inhibitor (ICI) therapies activate the immune system to unmask cancer cells that the body might otherwise not detect. These cancer therapies alter the immune system at different "checkpoint" proteins such as PD-1, PD-L1, or CTLA-4 to better target tumor cells, but also have the potential to affect normal tissues. In patients receiving ICI therapy, cutaneous reactions have been frequently documented, ranging from mild urticarial rashes to widespread cutaneous necrosis. Proper identification and management of ICI therapy side effects is essential to the care of these patients.

Immune checkpoints regulate acute myeloid leukemia stem cells.

Acute myeloid leukemia stem cells (LSCs) express major histocompatibility complex (MHC) class I and II and many different immune checkpoint ligands and receptors, in which respect they resemble professional antigen-presenting cells. In addition, LSCs reside in the bone marrow (BM), a primary and secondary lymphoid organ, surrounded by immune cells. The function of these immune checkpoints (ICs) in the regulation of an anti-tumor immune response is well studied and IC inhibitors (ICIs) became a standard of care in many solid tumors. However, ICIs have very limited efficacy in AML. Nevertheless,

Expression level of immune checkpoint inhibitory factors in preeclampsia.

Preeclampsia (PE) is a severe complication in pregnancy, and its symptoms (proteinuria and hypertension) manifest after 20 weeks of gestation, affecting up to 8 % of pregnancies. The pregnant women's immune system uses different tolerance mechanisms to deal with a semi-allogeneic fetus. The T-cell subsets including CD8+, CD4+, and Treg play a critical role in maintaining pregnancies. The expression of immune checkpoint molecules in T-cells can ensure pregnancy at the feto-maternal interface by controlling immune responses. This research aims to evaluate the expression level of immune checkpoin