Promising dawn in tumor microenvironment therapy: engineering oral bacteria

International Journal of Oral Science, Год журнала: 2024, Номер 16(1)

Опубликована: Март 13, 2024

Abstract Despite decades of research, cancer continues to be a major global health concern. The human mouth appears multiplicity local environments communicating with other organs and causing diseases via microbes. Nowadays, the role oral microbes in development progression has received increasing scrutiny. At same time, bioengineering technology nanotechnology is growing rapidly, which physiological activities natural bacteria are modified improve therapeutic efficiency cancers. These engineered were transformed achieve directed genetic reprogramming, selective functional reorganization precise control. In contrast endotoxins produced by typical genetically bacteria, flora exhibits favorable biosafety characteristics. To outline current cognitions upon microbes, cancers, related literatures searched reviewed based on PubMed database. We focused number mechanisms associated tumor microenvironment, involve occurrence development. Whether engineering can possible application therapy worth consideration. A deeper understanding relationship between may enhance our knowledge pathogenesis thus providing new insights strategies for prevention treatment.

Язык: Английский

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Exploiting the therapeutic implications of KRAS inhibition on tumor immunity

Cancer Cell, Год журнала: 2024, Номер 42(3), С. 338 - 357

Опубликована: Март 1, 2024

SummaryOver the past decade, RAS oncogenic proteins have transitioned from being deemed undruggable to having two clinically approved drugs, with several more in advanced stages of development. Despite initial benefit KRAS-G12C inhibitors for patients tumors harboring this mutation, rapid emergence drug resistance underscores urgent need synergize these other therapeutic approaches improve outcomes. mutant tumor cells can create an immunosuppressive microenvironment (TME), suggesting increased susceptibility immunotherapies following inhibition. This provides a rationale combining inhibitory drugs immune checkpoint blockade (ICB). However, achieving synergy clinical setting has proven challenging. Here, we explore how understanding impact on TME guide innovative inhibition immunotherapies, review progress both pre-clinical and stages, discuss challenges future directions.

Язык: Английский

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Cold and hot tumors: from molecular mechanisms to targeted therapy

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Окт. 18, 2024

Immunotherapy has made significant strides in cancer treatment, particularly through immune checkpoint blockade (ICB), which shown notable clinical benefits across various tumor types. Despite the transformative impact of ICB treatment therapy, only a minority patients exhibit positive response to it. In with solid tumors, those who respond well typically demonstrate an active profile referred as "hot" (immune-inflamed) phenotype. On other hand, non-responsive may distinct "cold" (immune-desert) phenotype, differing from features tumors. Additionally, there is more nuanced "excluded" positioned between and categories, known type. Effective differentiation understanding intrinsic factors, characteristics, TME, external factors are critical for predicting results. It widely accepted that therapy exerts profound effect on limited efficacy against or "altered" necessitating combinations therapeutic modalities enhance cell infiltration into tissue convert tumors ones. Therefore, aligning traits this review systematically delineates respective influencing extensively discusses varied approaches drug targets based assess efficacy.

Язык: Английский

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New insight in immunotherapy and combine therapy in colorectal cancer

Frontiers in Cell and Developmental Biology, Год журнала: 2025, Номер 12

Опубликована: Янв. 7, 2025

The advent of immune checkpoint inhibitors (ICIs) in colorectal cancer (CRC) treatment marks a major breakthrough. These therapies have proven safer and more effective than traditional radiotherapy targeted treatments. Immunotherapies like pembrolizumab, nivolumab, ipilimumab pioneered new avenues, potentially improving patient outcomes quality life. Additionally, advances immunotherapy prompted detailed research into CRC therapies, especially those integrating ICIs with conventional treatments, providing hope for patients shaping future practice. This review delves the mechanisms various evaluates their therapeutic potential when combined radiotherapy, chemotherapy, clinical settings. It also sheds light on current application involving treatment.

Язык: Английский

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KRAS inhibitors: resistance drivers and combinatorial strategies

Trends in cancer, Год журнала: 2024, Номер unknown

Опубликована: Дек. 1, 2024

Язык: Английский

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Analysis of ICIs alone or in combination rechallenged outcomes after progression from first-line ICIs plus chemotherapy in patients with advanced non-small cell lung cancer

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 2, 2025

Язык: Английский

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Targeting Immune Checkpoint Inhibitors for Non-Small-Cell Lung Cancer: Beyond PD-1/PD-L1 Monoclonal Antibodies

Cancers, Год журнала: 2025, Номер 17(5), С. 906 - 906

Опубликована: Март 6, 2025

Non-small-cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide. Immunotherapy targeting the PD-1/PD-L1 axis has revolutionized treatment, providing durable responses in subset patients. However, with fewer than 50% patients achieving significant benefits, there is critical need to expand therapeutic strategies. This review explores emerging targets immune checkpoint inhibition beyond PD-1/PD-L1, including CTLA-4, TIGIT, LAG-3, TIM-3, NKG2A, and CD39/CD73. We highlight biological basis CD8 T cell exhaustion shaping antitumor response. Novel approaches additional inhibitory receptors (IR) are discussed, focus on their distinct mechanisms action combinatory potential existing therapies. Despite advancements, challenges remain overcoming resistance optimizing patient selection. underscores importance dual blockade innovative bispecific antibody engineering maximize outcomes for NSCLC

Язык: Английский

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Association of type 2 diabetes, hypertension, and hyperlipidemia with immune-related adverse events in patients undergoing immune checkpoint inhibitors therapy

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Март 7, 2025

Aims Immune-related adverse events (irAEs) pose a significant challenge to the clinical use of immune checkpoint inhibitors (ICIs) in cancer immunotherapy. This study aims determine whether comorbid conditions such as type 2 diabetes (T2DM), hypertension, and hyperlipidemia affect risk irAEs patients receiving ICIs treatments. Materials methods We conducted retrospective analysis data from 3,489 treated with (anti-PD-1, anti-PD-L1, anti-CTLA-4) at West China Hospital Sichuan University 2017 2022. Logistic regression models were used evaluate associations between T2DM, irAEs. Subgroup analyses assessed without these comorbidities across different types. Additionally, we explored affecting organs. Results The results showed that significantly increased all types (T2DM: OR=1.40, 95% CI: 1.12-1.74, p=0.003; hypertension: OR=1.21, 1.00-1.45, p=0.049; hyperlipidemia: OR=1.62, 1.02-2.53, p=0.038). T2DM primarily lung (OR = 1.50, 1.12-2.01, FDR-adjusted p 0.036), three elevated cardiac Conclusions Our is first confirm an association occurrence therapy. finding highlights critical need for clinicians perform comprehensive evaluations patients’ prior treatment.

Язык: Английский

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Gastrointestinal toxicities associated with immune checkpoint inhibitors therapy: risks and management

Immunotherapy, Год журнала: 2025, Номер unknown, С. 1 - 11

Опубликована: Март 7, 2025

Immune checkpoint inhibitors (ICIs) have greatly improved cancer treatment by boosting the immune system's ability to target tumors. However, they can also cause serious side effects, particularly in digestive system. These include immune-related diarrhea, inflammation of intestines and, less commonly, stomach or esophagus. This review underscores importance early detection, accurate diagnosis, and timely improve patient outcomes. It highlights need for further research develop strategies reduce gastrointestinal toxicities enhance overall effectiveness ICIs therapy.

Язык: Английский

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Immune checkpoint blockade in hematological malignancies: current state and future potential

Frontiers in Oncology, Год журнала: 2024, Номер 14

Опубликована: Янв. 23, 2024

Malignant cells are known to evade immune surveillance by engaging checkpoints which negative regulators of the system. By restoring T-lymphocyte mediated anti-tumor effect, checkpoint inhibitors (ICI) have revolutionized treatment solid tumors but met rather modest success in hematological malignancies. Currently, only FDA approved indications for ICI therapy classic hodgkin lymphoma and primary mediastinal B cell lymphoma. Multiple clinical trials assessed alone combination with standard care treatments other lymphomas, plasma neoplasms myeloid were noted limited efficacy. These mostly focused on PD-1/PDL-1 CTLA-4 inhibitors. Recently, there has been an effort target like LAG-3, TIM-3, TIGIT along improving strategies inhibition. Drugs targeting macrophage checkpoint, CD47, also being tested. Long term safety efficacy data from these ongoing studies eagerly awaited. In this comprehensive review, we discuss mechanism inhibitors, key takeaways reported results completed therapies context

Язык: Английский

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