Predictive Biomarkers for Checkpoint Inhibitor Immune-Related Adverse Events

Cancers, Год журнала: 2023, Номер 15(5), С. 1629 - 1629

Опубликована: Март 6, 2023

Immune-checkpoint inhibitors (ICIs) are antagonists of inhibitory receptors in the immune system, such as cytotoxic T-lymphocyte-associated antigen-4, programmed cell death protein-1 and its ligand PD-L1, they increasingly used cancer treatment. By blocking certain suppressive pathways, ICIs promote T-cell activation antitumor activity but may induce so-called immune-related adverse events (irAEs), which mimic traditional autoimmune disorders. With approval more ICIs, irAE prediction has become a key factor improving patient survival quality life. Several biomarkers have been described potential predictors, some them already available for clinical use others under development; examples include circulating blood counts ratios, expansion diversification, cytokines, autoantibodies autoantigens, serum other biological fluid proteins, human leucocyte antigen genotypes, genetic variations gene profiles, microRNAs, gastrointestinal microbiome. Nevertheless, it is difficult to generalize application based on current evidence because most studies retrospective, time-limited restricted specific type cancer, or ICI. Long-term prospective cohorts real-life needed assess predictive capacity different biomarkers, regardless ICI type, organ involved site.

Язык: Английский

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Metabolic reprogramming in the tumor microenvironment of liver cancer

Journal of Hematology & Oncology, Год журнала: 2024, Номер 17(1)

Опубликована: Янв. 31, 2024

The liver is essential for metabolic homeostasis. onset of cancer often accompanied by dysregulated function, leading to rearrangements. Overwhelming evidence has illustrated that cellular metabolism can, in turn, promote anabolic growth and tumor propagation a hostile microenvironment. In addition supporting continuous survival, disrupted process also creates obstacles the anticancer immune response restrains durable clinical remission following immunotherapy. this review, we elucidate communication between cells their surrounding discuss how reprogramming impacts microenvironment efficacy We describe crucial role gut-liver axis remodeling crosstalk surveillance escape, highlighting novel therapeutic opportunities.

Язык: Английский

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Modulating gut microbiome in cancer immunotherapy: Harnessing microbes to enhance treatment efficacy

Cell Reports Medicine, Год журнала: 2024, Номер 5(4), С. 101478 - 101478

Опубликована: Апрель 1, 2024

Immunotherapy has emerged as a robust approach against cancer, yet its efficacy varied among individuals, accompanied by the occurrence of immune-related adverse events. As result, immunotherapy is far from satisfactory, and enormous efforts have been invested to develop strategies improve patient outcomes. The gut microbiome now well acknowledged for critical role in immunotherapy, with better understanding on host-microbes interaction context cancer treatment. Also, an increasing number trials conducted evaluate potential feasibility microbiome-targeting approaches enhance treatment patients. Here, metabolites (e.g., short-chain fatty acids, tryptophan metabolites) underlying mechanisms are explored. application that aim fecal microbiota transplantation, probiotics, dietary intervention) also elaborated, further discussion current challenges suggestions future research.

Язык: Английский

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Tumor immunotherapy resistance: Revealing the mechanism of PD-1 / PD-L1-mediated tumor immune escape

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 171, С. 116203 - 116203

Опубликована: Янв. 26, 2024

Tumor immunotherapy, an innovative anti-cancer therapy, has showcased encouraging outcomes across diverse tumor types. Among these, the PD-1/PD-L1 signaling pathway is a well-known immunological checkpoint, which significant in regulation of immune evasion by tumors. Nevertheless, considerable number patients develop resistance to anti-PD-1/PD-L1 rendering it ineffective long run. This research focuses on exploring factors PD-1/PD-L1-mediated immunotherapy. Initially, characterized its role facilitating evasion, emphasizing autoimmune homeostasis. Next, primary mechanisms PD-1/PD-L1-based immunotherapy are analyzed, including antigen deletion, T cell dysfunction, increased immunosuppressive cells, and alterations expression PD-L1 within cells. The possible ramifications altered metabolism, microbiota, DNA methylation also described. Finally, resolution strategies for dealing with discussed, placing particular emphasis personalized therapeutic approaches exploration more potent regimens.

Язык: Английский

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A gut microbial signature for combination immune checkpoint blockade across cancer types

Nature Medicine, Год журнала: 2024, Номер 30(3), С. 797 - 809

Опубликована: Март 1, 2024

Abstract Immune checkpoint blockade (ICB) targeting programmed cell death protein 1 (PD-1) and cytotoxic T lymphocyte 4 (CTLA-4) can induce remarkable, yet unpredictable, responses across a variety of cancers. Studies suggest that there is relationship between cancer patient’s gut microbiota composition clinical response to ICB; however, defining microbiome-based biomarkers generalize cohorts has been challenging. This may relate previous efforts quantifying species (or higher taxonomic rank) abundances, whereas microbial functions are often strain specific. Here, we performed deep shotgun metagenomic sequencing baseline fecal samples from unique, richly annotated phase 2 trial cohort patients with diverse rare cancers treated combination ICB ( n = 106 discovery cohort). We demonstrate strain-resolved abundances improve machine learning predictions 12-month progression-free survival relative models built using species-rank quantifications or comprehensive pretreatment factors. Through meta-analysis metagenomes further six comparable studies 364 validation cohort), found cross-cancer (and cross-country) validity strain–response signatures, but only when the training test used concordant regimens (anti-PD-1 monotherapy anti-PD-1 plus anti-CTLA-4). suggests future development microbiome diagnostics therapeutics should be tailored according treatment regimen rather than type.

Язык: Английский

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Critical role of the gut microbiota in immune responses and cancer immunotherapy

Journal of Hematology & Oncology, Год журнала: 2024, Номер 17(1)

Опубликована: Май 14, 2024

The gut microbiota plays a critical role in the progression of human diseases, especially cancer. In recent decades, there has been accumulating evidence connections between and cancer immunotherapy. Therefore, understanding functional regulating immune responses to immunotherapy is crucial for developing precision medicine. this review, we extract insights from state-of-the-art research decipher complicated crosstalk among microbiota, systemic system, context Additionally, as can account immune-related adverse events, discuss potential interventions minimize these effects clinical application five microbiota-targeted strategies that precisely increase efficacy Finally, holds promising target immunotherapeutics, summarize current challenges provide general outlook on future directions field.

Язык: Английский

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Biomarkers and prognostic factors of PD-1/PD-L1 inhibitor-based therapy in patients with advanced hepatocellular carcinoma

Biomarker Research, Год журнала: 2024, Номер 12(1)

Опубликована: Фев. 14, 2024

Abstract Systemic therapies using programmed death-1 (PD-1) and death ligand 1 (PD-L1) inhibitors have demonstrated commendable efficacy in some patients with advanced hepatocellular carcinoma (HCC); however, other individuals do not respond favorably. Hence, identifying the biomarkers, prognostic factors, their underlying mechanisms is crucial. In this review, we summarized latest advancements field. Within tumor microenvironment, PD-L1 expression commonly utilized to predict response. Moreover, characteristics of tumor-infiltrating lymphocytes are associated effectiveness immunotherapy. Preclinical studies identified stimulatory dendritic cells, conventional macrophages as potential biomarkers. The emergence single-cell sequencing spatial transcriptomics has provided invaluable insights into heterogeneity through lens profiling distribution. With widespread adoption next-generation sequencing, certain genomic characteristics, including mutational burden, copy number alterations, specific genes (TP53, CTNNB1, GZMB), signaling pathways (WNT/β-catenin) been found correlate prognosis. Furthermore, clinical features such size, number, metastasis status value. Notably, common indicators Child-Pugh score Eastern Cooperative Oncology Group score, which used liver diseases, shown potential. Similarly, employed laboratory parameters baseline transforming growth factor beta, lactate dehydrogenase, dynamic changes alpha-fetoprotein (AFP) abnormal prothrombin, CRAFITY (composed C-reactive protein AFP), immune adverse events predictive Novel imaging techniques EOB-MRI PET/CT employing innovative tracers also liquid biopsy gained use biomarker owing its non-invasive, convenient, highly reproducible nature, well monitoring capabilities. Research on gut microbiome, composition, changes, metabolomic analysis, considerable attention. Efficient discovery relies continuous updating treatment strategies. Next, recent research HCC immunotherapy an overview ongoing trials for contributing understanding improvement

Язык: Английский

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Immunosuppressive tumor microenvironment in the progression, metastasis, and therapy of hepatocellular carcinoma: from bench to bedside

Experimental Hematology and Oncology, Год журнала: 2024, Номер 13(1)

Опубликована: Авг. 1, 2024

Abstract Hepatocellular carcinoma (HCC) is a highly heterogeneous malignancy with high incidence, recurrence, and metastasis rates. The emergence of immunotherapy has improved the treatment advanced HCC, but problems such as drug resistance immune-related adverse events still exist in clinical practice. immunosuppressive tumor microenvironment (TME) HCC restricts efficacy essential for progression metastasis. Therefore, it necessary to elucidate mechanisms behind TME develop apply immunotherapy. This review systematically summarizes pathogenesis formation TME, by which accelerates We also status further discuss existing challenges potential therapeutic strategies targeting TME. hope inspire optimizing innovating immunotherapeutic comprehensively understanding structure function HCC.

Язык: Английский

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Role of the Microbiome and Diet for Response to Cancer Checkpoint Immunotherapy: A Narrative Review of Clinical Trials

Current Oncology Reports, Год журнала: 2025, Номер unknown

Опубликована: Янв. 3, 2025

The advent of checkpoint immunotherapy has dramatically changed the outcomes for patients with cancer. However, a considerable number have little or no response to therapy. We review recent findings on connection between gut microbiota and immune system, exploring whether this link could enhance effectiveness immunotherapy. Clinical studies reported specific types bacteria in larger quantities at baseline responders than non-responders, especially Akkermansia mucinifila, Ruminococcaceae, Faecalibacterium, Lachnospiraceae. Following consumption high-fiber diet, ferment dietary fiber short-chain fatty acids (SCFAs), like acetate, propionate, butyrate. Some SCFAs nurture intestinal epithelial cells, some enter bloodstream. Here can activate DC8 + cytotoxic T-cells induce cancer cell death. High intake diet was associated reduced risk progression death during Recent demonstrate that plant-based diets such as Mediterranean Diet positively influence whereas antibiotics proton pump inhibitors negatively by changing microbiota. This narrative provides evidence an association their metabolites favorable responses Prospective clinical trials are needed determine if interventions improve treatment outcomes.

Язык: Английский

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Gut microbiome and immune checkpoint inhibitor toxicity

European Journal of Cancer, Год журнала: 2025, Номер 216, С. 115221 - 115221

Опубликована: Янв. 5, 2025

Язык: Английский

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