Enhancing cancer immunotherapy via inhibition of soluble epoxide hydrolase

Proceedings of the National Academy of Sciences, Год журнала: 2024, Номер 121(7)

Опубликована: Фев. 8, 2024

Cancer therapy, including immunotherapy, is inherently limited by chronic inflammation-induced tumorigenesis and toxicity within the tumor microenvironment. Thus, stimulating resolution of inflammation may enhance immunotherapy improve immune checkpoint inhibition (ICI). As epoxy-fatty acids (EpFAs) are degraded enzyme soluble epoxide hydrolase (sEH), sEH increases endogenous EpFA levels to promote cancer-associated inflammation. Here, we demonstrate that systemic treatment with ICI induces expression in multiple murine cancer models. Dietary omega-3 polyunsaturated fatty acid supplementation pharmacologic inhibition, both alone combination, significantly anti-tumor activity these Notably, pharmacological abrogation pathway or combination counter-regulates an ICI-induced pro-inflammatory pro-tumorigenic cytokine storm. modulating through dietary represent a unique strategy paradigm therapies.

Язык: Английский

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Polymyalgia rheumatica and giant cell arteritis induced by immune checkpoint inhibitors: A systematic literature review highlighting differences from the idiopathic forms

Autoimmunity Reviews, Год журнала: 2024, Номер 23(7-8), С. 103589 - 103589

Опубликована: Июль 1, 2024

Язык: Английский

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Immunotherapy for early-stage non-small cell lung cancer: A system review

Journal of Cancer Research and Therapeutics, Год журнала: 2023, Номер 19(4), С. 849 - 865

Опубликована: Авг. 1, 2023

ABSTRACT With the addition of immunotherapy, lung cancer, one most common cancers with high mortality rates, has broadened treatment landscape. Immune checkpoint inhibitors have demonstrated significant efficacy in non-small cell cancer (NSCLC) and are now used as first-line therapy for metastatic disease, consolidation after radiotherapy unresectable locally advanced adjuvant surgical resection chemotherapy resectable disease. The use neoadjuvant immunotherapy patients early-stage NSCLC, however, is still debatable. We will address several aspects, namely initial monotherapy, combination chemotherapy, immunotherapy-related biomarkers, adverse effects, ongoing randomized controlled trials, current issues future directions NSCLC be discussed here.

Язык: Английский

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Tracking in situ checkpoint inhibitor-bound target T cells in patients with checkpoint-induced colitis

Cancer Cell, Год журнала: 2024, Номер 42(5), С. 797 - 814.e15

Опубликована: Май 1, 2024

The success of checkpoint inhibitors (CPIs) for cancer has been tempered by immune-related adverse effects including colitis. CPI-induced colitis is hallmarked expansion resident mucosal IFNγ cytotoxic CD8+ T cells, but how these arise unclear. Here, we track CPI-bound cells in intestinal tissue using multimodal single-cell and subcellular spatial transcriptomics (ST). Target occupancy was increased inflamed tissue, with drug-bound located distinct microdomains distinguished specific intercellular signaling transcriptional gradients. were largely CD4+ enrichment peripheral helper, follicular regulatory cells. emerged from both tissue-resident memory (TRM) populations, displayed more restricted target profiles, co-localized damaged epithelial lacking effective cues. Our analysis identifies causal pathways constitutes a resource to inform novel preventive strategies.

Язык: Английский

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Checkpoint Inhibitor-Induced Colitis: From Pathogenesis to Management

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(14), С. 11504 - 11504

Опубликована: Июль 15, 2023

The advent of immunotherapy, specifically immune checkpoint inhibitors (ICIs), for the treatment solid tumors has deeply transformed therapeutic algorithms in medical oncology. Approximately one-third patients treated with ICIs may de velop immune-related adverse events, and gastrointestinal tract is often affected by different grades mucosal inflammation. Checkpoint colitis (CIC) presents watery or bloody diarrhea and, case severe symptoms, requires discontinuation. pathogenesis CIC multifactorial still partially unknown: anti-tumor activity that collaterally effects colonic tissue upregulation specific systemic inflammatory pathways (i.e., CD8+ cytotoxic CD4+ T lymphocytes) are mainly involved. Many questions remain regarding timing options, biological treatment, especially anti-TNF alpha, can be offered to these aim rapidly resuming oncological therapies. shares similar aspects bowel disease (IBD) use ICI IBD under evaluation. This review aims summarize pathogenetic mechanism underlying discuss current evidenced-based management including role therapy, emphasizing relevant clinical impact on need prompt recognition treatment.

Язык: Английский

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Is 18F-FDG-PET/CT an Optimal Imaging Modality for Detecting Immune-Related Adverse Events after Immune-Checkpoint Inhibitor Therapy? Pros and Cons

Cancers, Год журнала: 2024, Номер 16(11), С. 1990 - 1990

Опубликована: Май 24, 2024

Immunotherapy with immune checkpoint inhibitors (ICIs) has revolutionized contemporary oncology, presenting efficacy in various solid tumors and lymphomas. However, ICIs may potentially overstimulate the system, leading to immune-related adverse events (irAEs). IrAEs affect multiple organs, such as colon, stomach, small intestine, kidneys, skin, lungs, joints, liver, lymph nodes, bone marrow, brain, heart, endocrine glands (e.g., pancreas, thyroid, or adrenal glands), exhibiting autoimmune inflammation. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) is commonly used oncology for staging assessment of therapy responses, but it also serve a tool detecting irAEs. This review aims present patterns metabolic activation associated irAEs due ICI treatment, identifiable through 18F-FDG PET/CT. It describes advantages early detection irAEs, presents challenges differentiating them from tumor progression. delves into aspects molecular response within context pseudoprogression hyperprogression, along typical imaging findings related these phenomena. Lastly, summarizes role functional PET oncological immunotherapy, speculating on its future significance limitations.

Язык: Английский

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Monitoring immunE DysregulAtion foLLowing Immune checkpOint-inhibitioN (MEDALLION): protocol for an observational cancer immunotherapy cohort study

BMC Cancer, Год журнала: 2024, Номер 24(1)

Опубликована: Июнь 14, 2024

Abstract Background Checkpoint inhibitors (CPIs) are widely used in cancer treatment, with transformative impacts on survival. They nonetheless carry a significant risk of toxicity the form immune-related adverse events (IrAEs), which may be sustained and life-altering. IrAEs require high-dose and/or prolonged steroid use represent healthcare burden. mimic immune-mediated inflammatory diseases (IMIDs) but understanding their pathogenesis is limited. The MEDALLION project aims to determine targetable mechanisms immune dysregulation IrAE development, employing an monitoring approach changes circulating tissue resident cells CPI recipients who do/do not develop them assessing contribution microbiome parallel. Methods non-randomised longitudinal cohort study aiming recruit 66 patient anti-PD1/PD-L1, anti-CTLA-4 or combination therapy. Eligible participants include those malignant melanoma adjuvant metastatic setting, mesothelioma non-small cell lung carcinoma (NSCLC) treated setting. Comprehensive clinical evaluation carried out alongside blood, skin swab stool sampling at time initiation (baseline) during subsequent routine hospital visits 6 occasions over 10-month follow-up period. It conservatively anticipated that one third enrolled patients will experience “significant IrAE” (SirAE), defined according pre-determined criteria specific affected tissue/organ system. Those developing such optionally undergo biopsy where appropriate, otherwise being managed standard care. Peripheral blood mononuclear analysed using multi-parameter flow cytometry investigate subsets, activation status cytokine profiles. Stool samples swabs DNA extraction for 16 S ribosomal RNA (rRNA) sequencing internal transcribed spacer (ITS) gene bacterial fungal diversity, respectively, including species associated toxicity. Stored biopsies available situ single-cell transcriptomic evaluation. Analysis focus identification biological predictors precursors SirAEs. Discussion assessed through cohort, potential tools prediction strategies targeted prevention treatment. Trial Registration was registered 18/09/2023 ISRCTN registry (43,419,676).

Язык: Английский

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The Benefits and Safety of Monoclonal Antibodies: Implications for Cancer Immunotherapy

Journal of Inflammation Research, Год журнала: 2025, Номер Volume 18, С. 4335 - 4357

Опубликована: Март 1, 2025

Monoclonal antibodies (mAbs) have transformed cancer treatment by providing highly targeted and effective therapies that specifically attack cells, thus reducing the likelihood of adverse events (AEs) in patients. mAbs exert their action through various mechanisms, such as receptor blockade, antibody-dependent cellular cytotoxicity (ADCC), complement-dependent (CDC), inhibition immune checkpoints (eg, PD-1, PD-L1, CTLA-4). These led to significant improvements several cancers, including HER2-positive breast cancer, non-small cell lung (NSCLC), melanoma. The efficacy mAb therapy is influenced intrinsic extrinsic factors, environmental exposures, psychosocial infection status, ways life, tumor microenvironment (TME), all which can impact responses outcomes. Notably, therapeutic benefits are often accompanied immune-related AEs (irAEs), vary from mild severe affect multiple organ systems. dual nature mAbs-stimulating antitumor while also inducing side effects-presents a notable challenge clinical practice. This review highlights importance proactive strategies for managing irAEs, early detection, corticosteroid use, immunosuppressive treatments, urgent need reliable predictive biomarkers improve Advancements prevention, prediction, management irAEs essential enhance safety effectiveness mAb-based therapies, ultimately aiming patient

Язык: Английский

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How to recognize and manage skin toxicities associated with immune checkpoint inhibitors: a practical approach

British Journal of Dermatology, Год журнала: 2023, Номер 189(Supplement_1), С. i3 - i10

Опубликована: Окт. 1, 2023

Abstract Immune checkpoint inhibitors (ICIs) have revolutionized treatment strategies in the field of oncology. Their favourable outcomes terms efficacy and side-effect profile can be thwarted by development immune-related adverse events (irAEs). Cutaneous irAEs are relatively common patients undergoing immunotherapy include inflammatory dermatoses (e.g. eczematous, psoriasiform lichenoid phenotypes), maculopapular eruptions, pruritus immunobullous disorders. Most these reactions managed without ICIs having to stopped completely; however, there some life-threatening toxicities that dermatologists oncologists should aware of. In this review, we focus on how recognize commonly associated cutaneous irAEs, touching upon rarer red flags; finally, provide guidance their management.

Язык: Английский

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Vitiligo-like Lesions as a Predictor of Response to Immunotherapy in Non-Small Cell Lung Cancer: Comprehensive Review and Case Series from a University Center

Current Oncology, Год журнала: 2024, Номер 31(2), С. 1113 - 1128

Опубликована: Фев. 19, 2024

The reference to vitiligo-like lesions (VLLs) induced by immune checkpoint inhibitors (ICIs) as a valuable predictive marker of treatment success immunotherapy with ICIs in melanoma has been mentioned the literature. Its role non-small cell lung cancer (NSCLC)-treated patients remains poorly recognized phenomenon uncertain significance regarding its value. A retrospective, observational, single-center report was performed, descriptive analysis clinicopathological and characteristics stage IV NSCLC who developed ICI-induced VLL between January 2018 December 2022, contextualized comprehensive review literature reported cases this phenomenon. During first 5 years’ experience ICI use treatment, three VLLs were diagnosed. In line previous reports, two presented exhibited response favorable prognosis. recognition understanding pathophysiological processes underlying may represent promising opportunity identify tumor ICIs, impact selection patient management. It also contribute new patterns molecular expression that could lead improvements therapeutic development.

Язык: Английский

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