Stratified analysis identifies HIF-2α as a therapeutic target for highly immune-infiltrated melanomas DOI Creative Commons
Amy Y. Huang, Kelly P. Burke, Ryan M. Porter

et al.

Published: Oct. 30, 2024

While immune-checkpoint blockade (ICB) has revolutionized treatment of metastatic melanoma over the last decade, identification broadly applicable robust biomarkers been challenging, driven in large part by heterogeneity ICB regimens and patient tumor characteristics. To disentangle these features, we performed a standardized meta-analysis eight cohorts patients treated with anti-PD-1 (n=290), anti-CTLA-4 (n=175), combination anti-PD-1/anti-CTLA-4 (n=51) RNA sequencing pre-treatment clinical annotations. Stratifying immune-high vs -low tumors, found that surprisingly, high immune infiltrate was biomarker for response to ICB, but not alone. Additionally, hypoxia-related signatures were associated non-response anti-PD-1, only amongst infiltrate-high melanomas. In cohort scRNA-seq melanoma, hypoxia also correlated immunosuppression changes tumor-stromal communication microenvironment (TME). Clinically actionable targets signaling uniquely expressed across different cell types. We focused on one such target, HIF-2

Language: Английский

Distinct CD8+ T cell dynamics associate with response to neoadjuvant cancer immunotherapies DOI Creative Commons

Housaiyin Li,

Dan P. Zandberg, Aditi Kulkarni

et al.

Cancer Cell, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

3
Dendritic cell maturation in cancer DOI
Chang Moon, Meriem Belabed, Matthew D. Park

et al.

Nature reviews. Cancer, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 7, 2025

Language: Английский

Citations

2
CD4+ T cells in antitumor immunity DOI Creative Commons
Elena Montauti, David Y. Oh, Lawrence Fong

et al.

Trends in cancer, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 1, 2024

Language: Английский

Citations

12
Neoadjuvant immune checkpoint blockade in women with mismatch repair deficient endometrial cancer: a phase I study DOI Creative Commons
Anneke L. Eerkens, Koen Brummel, Annegé Vledder

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Sept. 3, 2024

Neoadjuvant immune checkpoint blockade (ICB) has shown unprecedented activity in mismatch repair deficient (MMRd) colorectal cancers, but its effectiveness MMRd endometrial cancer (EC) remains unknown. In this investigator-driven, phase I, feasibility study (NCT04262089), 10 women with EC of any grade, planned for primary surgery, received two cycles neoadjuvant pembrolizumab (200 mg IV) every three weeks. A pathologic response (primary objective) was observed 5/10 patients, 2 patients showing a major response. No patient achieved complete partial radiologic (secondary 3/10 had stable disease and 2/10 were non-evaluable on magnetic resonance imaging. All completed treatment without severe toxicity (exploratory objective). At median duration follow-up 22.5 months, non-responders experienced recurrence. In-depth analysis the loco-regional systemic (predefined exploratory showed that monoclonal T cell expansion significantly correlated Tumour-draining lymph nodes displayed clonal overlap intra-tumoural expansion. pre-specified endpoints, efficacy terms as endpoint, secondary outcome safety tolerability reached. ICB proved safe induced pathologic, radiologic, immunologic responses EC, warranting further exploration extended treatment.

Language: Английский

Citations

6
Trem2-expressing multinucleated giant macrophages are a biomarker of good prognosis in head and neck squamous cell carcinoma DOI Creative Commons
Grégoire Gessain,

Ahmed-Amine Anzali,

Marvin Lerousseau

et al.

Cancer Discovery, Journal Year: 2024, Volume and Issue: 14(12), P. 2352 - 2366

Published: Sept. 13, 2024

Abstract Patients with head and neck squamous cell carcinomas (HNSCC) often have poor outcomes due to suboptimal risk management treatment strategies; yet integrating novel prognostic biomarkers into clinical practice is challenging. Here, we report the presence of multinucleated giant cells (MGC)—a type macrophages—in tumors from patients HNSCC, which are associated a favorable prognosis in treatment-naive preoperative chemotherapy–treated patients. Importantly, MGC density increased following therapy, suggesting role these antitumoral response. To enable translation as marker, developed deep-learning model automate its quantification on routinely stained pathological whole slide images. Finally, used spatial transcriptomic proteomic approaches describe MGC-related tumor microenvironment observed an increase central memory CD4 T cells. We defined MGC-specific signature resembling TREM2-expressing mononuclear tumor-associated macrophages, colocalized keratin niches. Significance: Novel individual needed guide therapeutic decisions for cancer. first time, granulomas macrophages keratin-rich niches, biomarker slides.

Language: Английский

Citations

4
GIMAP1 interacts with TMX1 to improve lung adenocarcinoma prognosis by influencing tumor immune microenvironment DOI

Pinglang Ruan,

Jiani Li,

Khalid A. Abdelhalim

et al.

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2025, Volume and Issue: 1871(3), P. 167661 - 167661

Published: Jan. 11, 2025

Language: Английский

Citations

0
Enhancing the effectiveness of immunotherapy in rheumatoid arthritis by delaying immunosenescence triggered by fibroblast-like synoviocytes DOI Creative Commons
Zhang Li, Yang Luo, Haili Shen

et al.

Journal of Orthopaedic Surgery and Research, Journal Year: 2025, Volume and Issue: 20(1)

Published: Jan. 23, 2025

Rheumatoid arthritis (RA) is a prevalent autoimmune disorder primarily targeting the diarthrodial joints. During progression of RA, fibroblast-like synoviocytes (FLSs) exhibit tumor-like behavior, including increased proliferation, inflammation mediation, and aggressive phenotypes, leading to bone erosion. Additionally, T cells in RA acquire pro-inflammatory characteristics, exacerbating inflammatory environment affected joints associated tissues. Notably, senescent contribute inflammation, further accelerating disease process. Metabolic changes rheumatoid FLSs not only maintain their properties but also trigger cascades, particularly affecting lymphocytes. This review examines molecular alterations context systemic immune aging, with focus on thymic insufficiency-associated cell senescence, explores potential therapeutic avenues.

Language: Английский

Citations

0
A pan-cancer analysis: predictive role of ZNF32 in cancer prognosis and immunotherapy response DOI Creative Commons

Minghan Li,

Chang Su,

Qianru Wang

et al.

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 27, 2025

The zinc finger protein 32 (ZNF32) has been associated with high expression in various cancers, underscoring its significant function both cancer biology and immune response. To further elucidate the biological role of ZNF32 identify potential immunotherapy targets cancer, we conducted an in-depth analysis ZNF32. We comprehensively investigated across tumors using diverse databases, including TCGA, CCLE, TIMER2.0, KM-Plotter, cBioPortal, ImmuCellAI. correlations between factors such as prognosis, infiltration, immunotherapy, DNA methylation, functions. Furthermore, performed vitro research to validate significance head neck (HNSC). Our study revealed that was types ACC, BRCA, others, indicating important a prognostic biomarker. Significant changes CNA methylation were expression. notably linked characteristics, cell MSI, TMB checkpoint gene expression, informing approaches. Interestingly, FaDu CAL27 lines, group elevated exhibited increased levels markers, CTLA-4 PD-L1. Overexpression significantly enhanced proliferation migration demonstrated through CCK-8 assays, colony formation, flow cytometry, Transwell migration, Boyden invasion assays. experiments confirmed promotes malignant behavior by driving HNSC migration. These results imply might be promising target for tumor prognosis immunotherapy. highlight tumorigenesis provide novel perspectives treatment strategies.

Language: Английский

Citations

0
Role of CD4+ T cells in cancer immunity: a single-cell sequencing exploration of tumor microenvironment DOI Creative Commons

Qi An,

Li Duan, Yuanyuan Wang

et al.

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

Published: Feb. 14, 2025

Recent oncological research has intensely focused on the tumor immune microenvironment (TME), particularly functions of CD4 + T lymphocytes. CD4+ lymphocytes have been implicated in antigen presentation, cytokine release, and cytotoxicity, suggesting their contribution to dynamics TME. Furthermore, application single-cell sequencing yielded profound insights into phenotypic diversity functional specificity cells In this review, we discuss current findings from analyses, emphasizing heterogeneity cell subsets implications immunology. addition, review critical signaling pathways molecular networks underpinning activities, thereby offering novel perspectives therapeutic targets strategies for cancer treatment prognosis.

Language: Английский

Citations

0
Somatostatin receptor-targeted polymeric nanoplatform for efficient CRISPR/Cas9 gene editing to enhance synergistic hepatocellular carcinoma therapy DOI Creative Commons
Suqin Zhang, Meng Li, Jingyi Zeng

et al.

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

Published: Feb. 20, 2025

The CRISPR/Cas9 system-based gene therapy can fundamentally address the issues of cancer occurrence, development, progression, and metastasis. However, lack targeting effectiveness hinders from entering clinical application. Herein, a somatostatin receptor-targeted polymeric nanoplatform is developed for delivery PD-L1-targeted system synergistic treatment hepatocellular carcinoma. This effectively incorporate chemotherapeutic drug paclitaxel to simultaneously biological safety packaging capacity viral vectors. After octreotide-modified polymer (LNA-PEG-OCT) guided nanoparticle into hepatoma carcinoma cells, protected ribonucleoprotein complex (RNP) achieved lysosomal escape. Then, RNP reached target (PD-L1) under guidance single guide RNA (sgRNA) in RNP. PD-L1 editing efficiency up 55.8% HepG2 cells vitro 46.0% tumor tissues vivo, leading effective suppression protein expression. Substantial inhibition cell proliferation further 79.45% growth repression against subcutaneous xenograft tumors were achieved. Overall, this not only provides promising nanocarrier delivery, but also expands potential combining chemotherapy.

Language: Английский

Citations

0