Multiple machine learning-based integrations of multi-omics data to identify molecular subtypes and construct a prognostic model for HNSCC DOI Creative Commons

Xiaoqin Luo,

Chao Li, Gang Qin

et al.

Hereditas, Journal Year: 2025, Volume and Issue: 162(1)

Published: Feb. 6, 2025

Abstract Background Immunotherapy has introduced new breakthroughs in improving the survival of head and neck squamous cell carcinoma (HNSCC) patients, yet drug resistance remains a critical challenge. Developing personalized treatment strategies based on molecular heterogeneity HNSCC is essential to enhance therapeutic efficacy prognosis. Methods We integrated four datasets (TCGA-HNSCC, GSE27020, GSE41613, GSE65858) from TCGA GEO databases. Using 10 multi-omics consensus clustering algorithms via MOVICS package, we identified two subtypes (CS1 CS2) validated their stability. A machine learning-driven prognostic signature was constructed by combining 101 algorithms, ultimately selecting 30 prognosis-related genes (PRGs) with Elastic Net model. This further linked immune infiltration, functional pathways, sensitivity. Results CS1 exhibited superior outcomes both META-HNSCC cohorts. The PRG-based stratified patients into low- high-risk groups, low-risk group showing prolonged survival, enhanced infiltration (B cells, T monocytes), activated functions (cytolytic activity, co-stimulation). High-risk were more sensitive radiotherapy chemotherapy (e.g., Cisplatin, 5-Fluorouracil), while responded better immunotherapy targeted therapies. Conclusion Our study delineates establishes robust model using data learning. These findings provide framework for selection, offering clinical insights optimize patients.

Language: Английский

Understanding the immunosuppressive microenvironment of glioma: mechanistic insights and clinical perspectives DOI Creative Commons

Hao Lin,

Chaxian Liu,

An-Kang Hu

et al.

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: May 8, 2024

Abstract Glioblastoma (GBM), the predominant and primary malignant intracranial tumor, poses a formidable challenge due to its immunosuppressive microenvironment, thereby confounding conventional therapeutic interventions. Despite established treatment regimen comprising surgical intervention, radiotherapy, temozolomide administration, exploration of emerging modalities such as immunotherapy integration medicine engineering technology therapy, efficacy these approaches remains constrained, resulting in suboptimal prognostic outcomes. In recent years, intensive scrutiny inhibitory milieu within GBM has underscored significance cellular constituents microenvironment their interactions with cells neurons. Novel immune targeted therapy strategies have emerged, offering promising avenues for advancing treatment. One pivotal mechanism orchestrating immunosuppression involves aggregation myeloid-derived suppressor (MDSCs), glioma-associated macrophage/microglia (GAM), regulatory T (Tregs). Among these, MDSCs, though constituting minority (4–8%) CD45 + GBM, play central component fostering evasion propelling tumor progression, angiogenesis, invasion, metastasis. MDSCs deploy intricate mechanisms that adapt dynamic (TME). Understanding interplay between provides compelling basis This review seeks elucidate inherent explore existing targets, consolidate insights into MDSC induction contribution immunosuppression. Additionally, comprehensively surveys ongoing clinical trials potential strategies, envisioning future where targeting could reshape landscape GBM. Through synergistic other modalities, this approach can establish multidisciplinary, multi-target paradigm, ultimately improving prognosis quality life patients

Language: Английский

Citations

62
Bispecific and multispecific antibodies in oncology: opportunities and challenges DOI

Maria-Elisabeth Goebeler,

Gernot Stuhler,

Ralf C. Bargou

et al.

Nature Reviews Clinical Oncology, Journal Year: 2024, Volume and Issue: 21(7), P. 539 - 560

Published: May 31, 2024

Language: Английский

Citations

35
Programmed death receptor (PD-)1/PD-ligand (L)1 in urological cancers : the “all-around warrior” in immunotherapy DOI Creative Commons
Qiang Liu,

Yujing Guan,

Shenglong Li

et al.

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Sept. 2, 2024

Programmed death receptor-1 (PD-1) and its ligand, programmed ligand-1 (PD-L1) are essential molecules that key in modulating immune responses. PD-L1 is constitutively expressed on various cells, epithelial cancer where it functions as a co-stimulatory molecule capable of impairing T-cell mediated Upon binding to PD-1 activated T-cells, the PD-1/PD-L1 interaction triggers signaling pathways can induce apoptosis or anergy, thereby facilitating escape tumors. In urological cancers, including bladder (BCa), renal cell carcinoma (RCC), prostate (PCa), upregulation has been demonstrated. It linked poor prognosis enhanced tumor evasion. Recent studies have highlighted significant role axis mechanisms cancers. The between T-cells further contributes immunosuppression by inhibiting activation proliferation. Clinical applications checkpoint inhibitors shown promising efficacy treating advanced significantly improving patient outcomes. However, resistance these therapies, either intrinsic acquired, remains challenge. This review aims provide comprehensive overview pathway We summarize regulatory mechanism underlying expression activity, genetic, epigenetic, post-transcriptional, post-translational modifications. Additionally, we discuss current clinical research inhibitors, their therapeutic potential, challenges associated with resistance. Understanding crucial for developing new strategies overcome limitations enhance immunotherapy.

Language: Английский

Citations

16
Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition DOI Creative Commons
Antonino Glaviano,

Hannah Lau,

Lukas M. Carter

et al.

Journal of Hematology & Oncology, Journal Year: 2025, Volume and Issue: 18(1)

Published: Jan. 13, 2025

The tumor microenvironment (TME) is integral to cancer progression, impacting metastasis and treatment response. It consists of diverse cell types, extracellular matrix components, signaling molecules that interact promote growth therapeutic resistance. Elucidating the intricate interactions between cells TME crucial in understanding progression challenges. A critical process induced by epithelial-mesenchymal transition (EMT), wherein epithelial acquire mesenchymal traits, which enhance their motility invasiveness progression. By targeting various components TME, novel investigational strategies aim disrupt TME's contribution EMT, thereby improving efficacy, addressing resistance, offering a nuanced approach therapy. This review scrutinizes key players emphasizing avenues therapeutically components. Moreover, article discusses implications for resistance mechanisms highlights current toward modulation along with potential caveats.

Language: Английский

Citations

12
Single-cell RNA sequencing and spatial transcriptomics of esophageal squamous cell carcinoma with lymph node metastases DOI Creative Commons
Wei Guo, Bolun Zhou,

Lizhou Dou

et al.

Experimental & Molecular Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Abstract Esophageal squamous cell carcinoma (ESCC) patients often face a grim prognosis due to lymph node metastasis. However, comprehensive understanding of the cellular and molecular characteristics metastatic nodes in ESCC remains elusive. In this study involving 12 patients, we employed single-cell sequencing, spatial transcriptomics (ST), multiplex immunohistochemistry (mIHC) explore attributes primary tumor samples, adjacent tissues, non-metastatic nodes. The analysis 161,333 cells revealed specific subclusters epithelial that were significantly enriched nodes, suggesting pro-metastatic characteristics. Furthermore, stromal microenvironment, including MMP3 + IL24 fibroblasts, APLN endothelial cells, CXCL12 pericytes, implicated metastasis through angiogenesis, collagen production, inflammatory responses. Exhausted CD8 T cycling status notably prevalent indicating their potential role facilitating We identified distinct cell-cell communication networks ligand-receptor pathways. Our findings validated transcriptome map mIHC. This enhances our comprehension aspects offering insights into novel therapeutic strategies for these individuals.

Language: Английский

Citations

3
The therapeutic potential of PD-1/PD-L1 pathway on immune-related diseases: Based on the innate and adaptive immune components DOI Open Access
Peng Zhang,

Yuting Wang,

Qianru Miao

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 167, P. 115569 - 115569

Published: Sept. 26, 2023

Currently, immunotherapy targeting programmed cell death 1 (PD-1) or ligand (PD-L1) has revolutionized the treatment strategy of human cancer patients. Meanwhile, PD-1/PD-L1 pathway also been implicated in pathogenesis many immune-related diseases, such as autoimmune chronic infection diseases and adverse pregnancy outcomes, by regulating components innate adaptive immune systems. Given power new therapy, a better understanding regulatory effects on responses will facilitate discovery novel biomarkers therapeutic drug targets. Targeting this may successfully halt potentially even reverse these pathological processes. In review, we discuss recent major advances axis diseases. We reveal that impact system is complex manifold multi-strategies targeted are taken Consequently, pathway, alone combination with other treatments, represent for future intervention

Language: Английский

Citations

23
Regulatory T cells in immune checkpoint blockade antitumor therapy DOI Creative Commons

An Zhang,

Tao Fan,

Yixiao Liu

et al.

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Nov. 8, 2024

Regulatory T cells (Tregs), an essential component of the human immune system, are a heterogeneous group lymphocytes with ability to suppress responses and maintain homeostasis. Recent evidence indicates that Tregs may impair antitumor immunity facilitate cancer progression by weakening functions effector (Teffs). Consequently, targeting eliminate them from tumor microenvironments improve Teffs' activity could emerge as effective strategy for immunotherapy. This review outlines biology Tregs, detailing their origins, classification, crucial markers. Our focus lies on complex role in cancer's development, treatment, particularly suppressive upon via multiple mechanisms. We delve into Tregs' involvement checkpoint blockade (ICB) therapy, dual effect immunotherapy potential biomarkers ICB therapy effectiveness. also summarize advances therapies adjust optimize which be devising innovative treatment strategies.

Language: Английский

Citations

14
The opportunities and challenges of using PD-1/PD-L1 inhibitors for leukemia treatment DOI
Mengdan Xu, Shenglong Li

Cancer Letters, Journal Year: 2024, Volume and Issue: 593, P. 216969 - 216969

Published: May 19, 2024

Language: Английский

Citations

11
Current Landscape of Cancer Immunotherapy: Harnessing the Immune Arsenal to Overcome Immune Evasion DOI Creative Commons
Ankita Mitra, Anoop Kumar, Nitin Amdare

et al.

Biology, Journal Year: 2024, Volume and Issue: 13(5), P. 307 - 307

Published: April 28, 2024

Cancer immune evasion represents a leading hallmark of cancer, posing significant obstacle to the development successful anticancer therapies. However, landscape cancer treatment has significantly evolved, transitioning into era immunotherapy from conventional methods such as surgical resection, radiotherapy, chemotherapy, and targeted drug therapy. Immunotherapy emerged pivotal component in treatment, harnessing body’s system combat offering improved prognostic outcomes for numerous patients. The remarkable success spurred efforts enhance clinical efficacy existing agents strategies. Several immunotherapeutic approaches have received approval treatments, while others are currently preclinical trials. This review explores recent progress unraveling mechanisms evaluates effectiveness diverse strategies, including vaccines, adoptive cell therapy, antibody-based treatments. It encompasses both established treatments those under investigation, providing comprehensive overview through immunological approaches. Additionally, article emphasizes current developments, limitations, challenges immunotherapy. Furthermore, by integrating analyses resistance exploring combination strategies personalized approaches, it offers valuable insights crucial novel

Language: Английский

Citations

10
IMbrave152/SKYSCRAPER-14: a Phase III study of atezolizumab, bevacizumab and tiragolumab in advanced hepatocellular carcinoma DOI Creative Commons
Shreya Badhrinarayanan,

Christopher Cotter,

Huaqi Zhu

et al.

Future Oncology, Journal Year: 2024, Volume and Issue: 20(28), P. 2049 - 2057

Published: June 10, 2024

Atezolizumab plus bevacizumab is a standard of care, first-line therapy for advanced hepatocellular carcinoma (HCC). Myeloid and T regulatory cells are key immunosuppressive cell types within the hepatic tumor microenvironment associated with clinical resistance to atezolizumab HCC overall poor prognosis. Therapeutic targeting TIGIT, which highly expressed in these cells, tiragolumab may overcome environment improve benefit, hypothesis supported by positive efficacy signals Phase Ib/II MORPHEUS-Liver study. This paper describes rationale design IMbrave152/SKYSCRAPER-14, randomized, double-blind, placebo-controlled III study comparing or placebo patients no prior systemic treatment.

Language: Английский

Citations

9