Current Treatment Options for Renal Cell Carcinoma: Focus on Cell-Based Immunotherapy DOI Open Access
Angela Hwang, Vedika Mehra,

Jyoti Chhetri

et al.

Cancers, Journal Year: 2024, Volume and Issue: 16(6), P. 1209 - 1209

Published: March 19, 2024

Renal cell carcinoma (RCC) affects over 400,000 patients globally each year, and 30% of present with metastatic disease. Current standard care therapy for RCC involve TKIs ICIs, including combinatorial strategies, but this offers only modest clinical benefit. Novel treatment approaches are warranted, cell-based immunotherapies hold significant promise. These currently being tested in the pre-clinical setting early phase trials. Here, we review landscape cellular immunotherapy context available therapies, a particular focus on defining current best antigenic targets, range products explored RCC, how advanced engineering solutions may further enhance these therapies space.

Language: Английский

Dynamics of tertiary lymphoid structures and immune cross talk in early versus advanced colorectal cancer: potential implications for immunotherapy DOI Creative Commons
Zixu Chen,

Bang Hu,

Keyu Cai

et al.

Cancer Immunology Immunotherapy, Journal Year: 2025, Volume and Issue: 74(6)

Published: April 26, 2025

Abstract Background Irrespective of microsatellite status, immune checkpoint inhibitor therapy shows superior efficacy in early-stage colorectal cancer (CRC) compared to advanced cases. The distinctions the tumor microenvironment (TME) and tertiary lymphoid structure (TLS) between early- advanced-stage CRC may represent a critical factor, yet remain incompletely elucidated. Methods We comprehensively analyzed single-cell RNA sequencing data, bulk transcription data pathological tissue investigate dynamic changes TME. features TLS tumors their potential impact on immunotherapy were explored using three in-house cohorts. Results provided fine maps landscape early CRC. Significant functional differences identified CD4 + Tfh BGC cells revealed CXCL13 expression CD8 Tex cells, along with CD40–CD40L interactions could be key regulators functionality subsequently affect response immunotherapy. Conclusions Our research shed light multilayered dysfunction elucidates alterations during progression CRC, providing insights for studies exploration target

Language: Английский

Citations

0
Spatially segregated APOE+ macrophages restrict immunotherapy efficacy in clear cell renal cell carcinoma DOI Creative Commons
Qintao Ge,

Jialin Meng,

Zhongyuan Wang

et al.

Theranostics, Journal Year: 2025, Volume and Issue: 15(11), P. 5312 - 5336

Published: April 13, 2025

Background: Immunotherapy has revolutionized cancer treatment and holds great potential for them, including metastatic clear cell renal carcinoma (ccRCC). However, immune resistance remains a major obstacle, limiting its efficacy durability. Understanding the mechanisms of tolerance in tumor microenvironment (TME) is pivotal overcoming these challenges enhancing therapeutic outcomes. Methods: Over 2000 samples, real-world cohort 230 advanced ccRCC patients treated with checkpoint blockade (ICB) were analyzed. Single-cell RNA sequencing data from 13 regions categorized into ICB-exposed, ICB-resistant, ICB-responsive groups. Multiple robust algorithms multiplex immunofluorescence used to explore TME composition macrophage heterogeneity. Spatial communication dynamics further investigated. In vitro experiments performed evaluate impact SPP1 on 786-O 769-P cells. Co-culture THP-1-derived macrophages, followed by Western blot, flow cytometry, functional assays, investigate SPP1-mediated polarization progression. Results: The results revealed an elevated presence Apolipoprotein E (APOE)+ macrophages ICB-resistant ccRCC. Notably, higher APOE+ proportion indicated shorter prognosis worse response ICB (P < 0.001). Elevated expression CCAAT Enhancer Binding Protein Delta (CEBPD) was markedly linked several immunosuppressive pathways, hindering T recruitment, promoting exhaustion, ultimately diminishing poorer efficacy. Meanwhile, upregulated Secreted Phosphoprotein 1 (SPP1) significantly enhances proliferation, clonal formation, migration Tumor-derived SPP1. Additionally, signaling malignant cells appeared recruit margins, promotes M2-like macrophages. vicinity tumor, shape releasing abundant TGF-β signals, anti-tumor effector activity tumors, contributing Conclusion: This study reveals critical role suppression therapy By exhaustion signaling, particularly via localized TGF-β, spatially segregated undermine Targeting especially conjunction ICB, presents promising strategy overcome enhance outcomes patients.

Language: Английский

Citations

0
Nervous system–gut microbiota–immune system axis: future directions for preventing tumor DOI Creative Commons
Juanjuan Wang,

Wenyue Cheng,

Rongcun Yang

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: May 1, 2025

Tumor is one of the leading causes death worldwide. The occurrence and development tumors are related to multiple systems factors such as immune system, gut microbiota, nervous system. system plays a critical role in tumor development. Studies have also found that microbiota can directly or indirectly affect tumorigenesis With increasing attention on microenvironment recent years, has emerged novel regulator Some therapies based been tested clinical trials. However, not only interact with cells but through microbiota. system-mediated regulate tumorigenesis, growth, invasion, metastasis Here, we mainly explore potential effects system-gut microbiota-immune axis involve regulating which prevent Meanwhile, direct regulation by development, reviewed.

Language: Английский

Citations

0
Tertiary lymphoid structures in gliomas: impact on tumour immunity and progression DOI Creative Commons
Jiatong Chen,

Yuechao Yang,

Shihai Luan

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: May 9, 2025

Tertiary lymphoid structures (TLSs) are ectopic formations that develop in chronically inflamed tissues, including various solid tumours. In the context of gliomas, presence TLSs has recently attracted considerable attention because their potential implications tumour immunology and therapy. The immune microenvironment (TIME) plays a crucial role cancer progression, tumour-infiltrating cells (TILs) key players this environment. These cell aggregates, known as TLSs, display distinct characteristics across different However, central nervous system (CNS) tumours highly heterogeneous, environment within these is often more deficient than peripheral tissue This leads to differences formation function CNS variations particularly relevant glioma immunotherapy could have important for treatment strategies. review focuses on composition examines complexity glioblastoma (GBM) microenvironment, highlights unique GBM, providing new theoretical insights practical foundations targeting immunotherapy.

Language: Английский

Citations

0
Current Treatment Options for Renal Cell Carcinoma: Focus on Cell-Based Immunotherapy DOI Open Access
Angela Hwang, Vedika Mehra,

Jyoti Chhetri

et al.

Cancers, Journal Year: 2024, Volume and Issue: 16(6), P. 1209 - 1209

Published: March 19, 2024

Renal cell carcinoma (RCC) affects over 400,000 patients globally each year, and 30% of present with metastatic disease. Current standard care therapy for RCC involve TKIs ICIs, including combinatorial strategies, but this offers only modest clinical benefit. Novel treatment approaches are warranted, cell-based immunotherapies hold significant promise. These currently being tested in the pre-clinical setting early phase trials. Here, we review landscape cellular immunotherapy context available therapies, a particular focus on defining current best antigenic targets, range products explored RCC, how advanced engineering solutions may further enhance these therapies space.

Language: Английский

Citations

2