Overcoming immunotherapy resistance in gastric cancer: insights into mechanisms and emerging strategies

Cell Death and Disease, Год журнала: 2025, Номер 16(1)

Опубликована: Фев. 7, 2025

Abstract Gastric cancer (GC) remains a leading cause of cancer-related mortality worldwide, with limited treatment options in advanced stages. Immunotherapy, particularly immune checkpoint inhibitors (ICIs) targeting PD1/PD-L1, has emerged as promising therapeutic approach. However, significant proportion patients exhibit primary or acquired resistance, limiting the overall efficacy immunotherapy. This review provides comprehensive analysis mechanisms underlying immunotherapy resistance GC, including role tumor microenvironment, dynamic PD-L1 expression, compensatory activation other checkpoints, and genomic instability. Furthermore, explores GC-specific factors such molecular subtypes, unique evasion mechanisms, impact Helicobacter pylori infection. We also discuss emerging strategies to overcome combination therapies, novel immunotherapeutic approaches, personalized based on genomics microenvironment. By highlighting these key areas, this aims inform future research directions clinical practice, ultimately improving outcomes for GC undergoing

Язык: Английский

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Reprogramming tumor-associated macrophages in gastric cancer: a pathway to enhanced immunotherapy

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Март 3, 2025

Gastric cancer (GC) remains a significant global health concern due to its poor prognosis and limited therapeutic options, particularly in advanced stages. Tumor microenvironment (TME), tumor-associated macrophages (TAMs), plays key role tumor progression, immune evasion, therapy resistance. TAMs exhibit plasticity, shifting between pro-inflammatory M1 immunosuppressive M2 phenotypes, with the latter predominating GC contributing outcomes. Recent advancements focus on targeting TAMs, including inhibiting polarization, reprogramming combining TAM-targeted approaches checkpoint inhibitors. Innovations nanotechnology, metabolic reprogramming, pathways such as interleukin-6 C-C motif ligand 2/C-C chemokine receptor 2 further enhance these strategies. However, challenges remain, spatial functional heterogeneity of within TME need for selective avoid disrupting homeostasis. Ongoing research TAM origins, functions, interactions is crucial developing precise effective therapies. These advances hold promise not only improving outcomes but also addressing other cancers similarly complex microenvironments.

Язык: Английский

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Tumour‐associated macrophages in gastric cancer: From function and mechanism to application

Clinical and Translational Medicine, Год журнала: 2023, Номер 13(8)

Опубликована: Авг. 1, 2023

Gastric cancer (GC) is a malignant tumour, with high morbidity and mortality rates worldwide. The occurrence development of GC complex process involving genetic changes in tumour cells the influence surrounding microenvironment (TME). Accumulative evidence shows that tumour-associated macrophages (TAMs) play vital role GC, acting as plentiful active infiltrating inflammatory TME.

Язык: Английский

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Complex Role of Regulatory T Cells (Tregs) in the Tumor Microenvironment: Their Molecular Mechanisms and Bidirectional Effects on Cancer Progression

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(13), С. 7346 - 7346

Опубликована: Июль 4, 2024

Regulatory T cells (Tregs) possess unique immunosuppressive activity among CD4-positive cells. Tregs are ubiquitously present in mammals and function to calm excessive immune responses, thereby suppressing allergies or autoimmune diseases. On the other hand, due their function, thought promote cancer progression. The tumor microenvironment (TME) is a multicellular system composed of many cell types, including cells, infiltrating cancer-associated fibroblasts (CAFs). Within this environment, recruited by chemokines metabolic factors impede effective anti-tumor responses. However, some cases, presence can also improve patient's survival rates. Their functional consequences may vary across locations, stages. An in-depth understanding precise roles mechanisms actions Treg crucial for developing treatments, emphasizing need further investigation validation. This review aims provide comprehensive overview complex multifaceted within TME, elucidating cellular communications, signaling pathways, impacts on progression highlighting potential through interactions with molecules.

Язык: Английский

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The Multifaceted Roles of BACH1 in Disease: Implications for Biological Functions and Therapeutic Applications

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Янв. 30, 2025

Abstract BTB domain and CNC homolog 1 (BACH1) belongs to the family of basic leucine zipper proteins is expressed in most mammalian tissues. It can regulate its own expression play a role transcriptionally activating or inhibiting downstream target genes. has crucial various biological processes, such as oxidative stress, cell cycle, heme homeostasis, immune regulation. Recent research highlights BACH1's significant regulatory roles series conditions, including stem pluripotency maintenance differentiation, growth, senescence, apoptosis. BACH1 closely associated with cardiovascular diseases contributes angiogenesis, atherosclerosis, restenosis, pathological cardiac hypertrophy, myocardial infarction, ischemia/reperfusion (I/R) injury. promotes tumor proliferation metastasis by altering metabolism epithelial‐mesenchymal transition phenotype. Moreover, appears show an adverse neurodegenerative diseases, gastrointestinal disorders, leukemia, pulmonary fibrosis, skin diseases. Inhibiting may be beneficial for treating these This review summarizes mechanism different types proposing that precise targeted intervention provide new strategies human disease prevention treatment.

Язык: Английский

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Anti-Tumor Effects and Toxicity Reduction Mechanisms of Prunella vulgaris: A Comprehensive Review

Molecules, Год журнала: 2024, Номер 29(8), С. 1843 - 1843

Опубликована: Апрель 18, 2024

Purpose: To investigate and systematically describe the mechanism of action Prunella vulgaris (P. vulgaris) against digestive system tumors related toxicity reduction. Methods: This study briefly describes history medicinal food pharmacological effects P. vulgaris, focusing on review anti-digestive tumor active ingredients its Results: The may exert anti-tumor by inducing apoptosis cancer cells, inhibiting angiogenesis, migration invasion autophagy. In addition, inhibit release inflammatory factors macrophages increase level indicators oxidative stress through modulation target genes in pathway to achieve effect Conclusion: medicine homology plant not only treat different mechanisms but also reduce toxic effects. is worthy being explored more deeply.

Язык: Английский

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Targeting tumor‑associated macrophages: Critical players in tumor progression and therapeutic strategies (Review)

International Journal of Oncology, Год журнала: 2024, Номер 64(6)

Опубликована: Апрель 30, 2024

Tumor‑associated macrophages (TAMs) are essential components of the tumor microenvironment (TME) and display phenotypic heterogeneity plasticity associated with stimulation bioactive molecules within TME. TAMs predominantly exhibit tumor‑promoting phenotypes involved in progression, such as angiogenesis, metastasis, immunosuppression resistance to therapies. In addition, have potential regulate cytotoxic elimination phagocytosis cancer cells interact other immune engage innate adaptive systems. this context, targeting has been a popular area research therapy, comprehensive understanding complex role progression exploration macrophage‑based therapeutic approaches for future therapeutics against cancers. The present review provided updated overview function summarized recent advances TAM‑targeting strategies discussed obstacles perspectives therapies

Язык: Английский

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Targeting amino acid metabolism to inhibit gastric cancer progression and promote anti-tumor immunity: a review

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Фев. 13, 2025

The incidence of gastric cancer remains high and poses a serious threat to human health. Recent comprehensive investigations into amino acid metabolism immune system components within the tumor microenvironment have elucidated functional interactions between cells, metabolism. This study reviews characteristics in cancer, with particular focus on methionine, cysteine, glutamic acid, serine, taurine, other acids. It discusses relationship these metabolic processes, development, body’s anti-tumor immunity, analyzes importance targeting for chemotherapy immunotherapy.

Язык: Английский

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Interactions between cancer cells and tumor-associated macrophages in tumor microenvironment

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Год журнала: 2025, Номер unknown, С. 189344 - 189344

Опубликована: Май 1, 2025

Язык: Английский

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Comprehensive integration of single-cell RNA and transcriptome RNA sequencing to establish a pyroptosis-related signature for improving prognostic prediction of gastric cancer

Computational and Structural Biotechnology Journal, Год журнала: 2024, Номер 23, С. 990 - 1004

Опубликована: Фев. 7, 2024

Cell pyroptosis, a Gasdermin-dependent programmed cell death characterized by inflammasome, plays complex and dynamic role in Gastric cancer (GC), serious threat to human health. Therefore, the value of pyroptosis-related genes (PRGs) as prognostic biomarkers therapeutic indicators for patients needs be exploited GC. This study integrates single-cell RNA sequencing (scRNA-seq) dataset GSE183904 with GC transcriptome data from TCGA database, focusing on expression distribution PRGs at level. The signature was established using Cox LASSO analyses. differences long-term prognosis, immune infiltration, mutation profile, CD274 response chemotherapeutic drugs between two groups were analyzed evaluated. A tissue array used verify six PRGs, CD274, CD163 FoxP3. C12orf75, VCAN, RGS2, MKNK2, SOCS3 TNFAIP2 successfully screened out establish potently predict survival time patients. webserver (https://pumc.shinyapps.io/GastricCancer/) prediction developed based this signature. High-risk score typically had worse prognoses, resistance classical chemotherapy, more immunosuppressive tumor microenvironment. greatly elevated while RGS2 MKNK2 decreased samples. Further, VCAN positively related infiltrations Tregs M2 TAMs TME cells. In summary, potent accurately forecast treatment responsiveness

Язык: Английский

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