Single-cell RNA sequencing and spatial transcriptomics of bladder Ewing sarcoma DOI Creative Commons
Weipu Mao, Kangjie Xu, Keyi Wang

et al.

iScience, Journal Year: 2024, Volume and Issue: 27(10), P. 110921 - 110921

Published: Sept. 12, 2024

Bladder Ewing sarcoma/primitive neuroectodermal tumor (bladder ES/PNET) is a rare and highly malignant associated with poor prognosis, yet its underlying mechanisms remain poorly understood. Here, we employed combination of single-cell RNA sequencing (scRNA-seq), spatial transcriptomics (ST), functional analyses to delve into the pathogenesis bladder ES/PNET. The investigation revealed presence specialized types epithelial cells (referred as ES-Epi) mast ES-Mast) within ES/PNET in comparison urothelial carcinoma. Notably, TNFRSF12A exhibited significant upregulation Furthermore, possessed ability activate through TNFSF12-TNFRSF12A ligand-receptor signaling pattern. In addition, Enavatuzumab can significantly inhibit migratory sarcoma cell line RD-ES. This groundbreaking study provides unprecedented mechanistic insights progression introduces potential therapeutic avenue for treating this challenging malignancy.

Language: Английский

Spatial landscapes of cancers: insights and opportunities DOI
Julia Chen, Ludvig Larsson, Alexander Swarbrick

et al.

Nature Reviews Clinical Oncology, Journal Year: 2024, Volume and Issue: 21(9), P. 660 - 674

Published: July 23, 2024

Language: Английский

Citations

20
Starfysh integrates spatial transcriptomic and histologic data to reveal heterogeneous tumor–immune hubs DOI Creative Commons
Siyu He, Yinuo Jin, Achille Nazaret

et al.

Nature Biotechnology, Journal Year: 2024, Volume and Issue: unknown

Published: March 21, 2024

Spatially resolved gene expression profiling provides insight into tissue organization and cell-cell crosstalk; however, sequencing-based spatial transcriptomics (ST) lacks single-cell resolution. Current ST analysis methods require RNA sequencing data as a reference for rigorous interpretation of cell states, mostly do not use associated histology images are capable inferring shared neighborhoods across multiple tissues. Here we present Starfysh, computational toolbox using deep generative model that incorporates archetypal any known type markers to characterize or new tissue-specific states without reference. Starfysh improves the characterization dynamics in complex tissues enables comparison niches hubs Integrative primary estrogen receptor (ER)-positive breast cancer, triple-negative cancer (TNBC) metaplastic (MBC) led identification with patient- disease-specific compositions revealed metabolic reprogramming shaping immunosuppressive aggressive MBC.

Language: Английский

Citations

19
Single-cell and spatial genomic landscape of non-small cell lung cancer brain metastases DOI
Andrea Califano, Lindsay Caprio, Amit Dipak Amin

et al.

Nature Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 27, 2025

Language: Английский

Citations

2
The CD58-CD2 axis is co-regulated with PD-L1 via CMTM6 and shapes anti-tumor immunity DOI Creative Commons
Patricia Ho, Johannes C. Melms,

Meri Rogava

et al.

Cancer Cell, Journal Year: 2023, Volume and Issue: 41(7), P. 1207 - 1221.e12

Published: June 15, 2023

Language: Английский

Citations

37
Adaptive immune receptor repertoire analysis DOI
Vanessa Mhanna, Habib Bashour, Khang Lê Quý

et al.

Nature Reviews Methods Primers, Journal Year: 2024, Volume and Issue: 4(1)

Published: Jan. 25, 2024

Language: Английский

Citations

12
Uveal melanoma immunogenomics predict immunotherapy resistance and susceptibility DOI Creative Commons
Shravan Leonard‐Murali, Chetana Bhaskarla,

Ghanshyam S. Yadav

et al.

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

Published: April 16, 2024

Abstract Immune checkpoint inhibition has shown success in treating metastatic cutaneous melanoma but limited efficacy against uveal melanoma, a rare variant arising from the immune privileged eye. To better understand this resistance, we comprehensively profile 100 human metastases using clinicogenomics, transcriptomics, and tumor infiltrating lymphocyte potency assessment. We find that over half of these harbor lymphocytes with potent autologous specificity, despite low mutational burden resistance to prior immunotherapies. However, observe strikingly intratumoral T cell receptor clonality within microenvironment even after harness quiescent lymphocytes, develop transcriptomic biomarker enable vivo identification ex liberation counter their growth suppression. Finally, demonstrate adoptive transfer transcriptomically selected can promote immunity patients when other immunotherapies are incapable.

Language: Английский

Citations

10
Importance of EQA/PT for the detection of genetic variants in comprehensive cancer genome testing DOI Creative Commons
Kazuyuki Matsushita, Takayuki Ishige, Kousuke Watanabe

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 7, 2025

Comprehensive genomic profiling (CGP) is increasingly used as a clinical laboratory test and being applied to cancer treatment; however, standardization external quality assessments (EQA) have not been fully developed. This study performed cost-effective EQA proficiency tests (PT) for CGP testing among multiple institutions those belong the working group of Japan Association Clinical Laboratory Science (JACLS). revealed that preanalytical processes, such derived nucleic acids (NA) extraction from formalin fixed paraffine embedded (FFPE) samples, are critical. First, with extracted DNA cell lines showed detection rate 100% (9 out 9) in KRAS (c.38G > A; p.G13D), PIK3CA (p.H1047R), B-Raf proto-oncogene, serine/threonine kinase (BRAF) (c.1799 T p.V600E) cases 10% variant allele frequency (VAF). However, BRAF decreased 67% (6 VAF 4.9%. Second, when was FFPE pathogenic variants companion diagnostic indications were detected all 10 participating laboratories. Each had < 20% VAFs on average (8.1–19.1%) wide variability laboratories observed (relative standard deviation, 13–60%). Nonetheless, (c.1798_1799delinsAA; p.V600K) 8.1% VAF, EGFR (c.2235_2249del; p.E746_A750del) 9.7% (c.2254_2277del; p.S752_I759del) 9.8% 70% (7/10), 60% (6/10) frequency, respectively. Therefore, pre-analytic processing critical analysis. Further, incorrect results reported case independent calling BRAF; c.1798_1799delinsAA (p.V600K) mistakenly interpreted c.1798G A, c.1799 A other strand. In conclusion, EQA/PT institutes common samples importance pre-analysis helped us understand significance pipeline pitfalls usually ignored by internal control single institute.

Language: Английский

Citations

1
The present and future of the Cancer Dependency Map DOI
Rand Arafeh, Tsukasa Shibue, Joshua M. Dempster

et al.

Nature reviews. Cancer, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 28, 2024

Language: Английский

Citations

8
Advances and applications in single-cell and spatial genomics DOI
Jingjing Wang, Fang Ye, Haoxi Chai

et al.

Science China Life Sciences, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 20, 2024

Language: Английский

Citations

7
CD58 alterations govern antitumor immune responses by inducing PD-L1 and IDO in diffuse large B-cell lymphoma DOI
Xiyue Xu, Yidan Zhang, Yaxiao Lu

et al.

Cancer Research, Journal Year: 2024, Volume and Issue: 84(13), P. 2123 - 2140

Published: Jan. 1, 2024

Recurrent abnormalities in immune surveillance-related genes affect the progression of diffuse large B-cell lymphoma (DLBCL) and modulate response to therapeutic interventions. CD58 interacts with CD2 receptor on T cells NK is recurrently mutated deleted DLBCL, suggesting that it may play a role regulating antitumor immunity. In this study, we comprehensively analyzed genomic characteristics through targeted next-generation sequencing, RNA sequencing (RNA-seq), whole-exome single-cell RNA-seq patients newly diagnosed DLBCL. The mutation rate was 9.1%, copy number loss 44.7% among all enrolled Notably, genetic alterations, along low expression, significantly correlated reduced rates R-CHOP therapy inferior progression-free survival overall survival. Single-cell revealed expression tumor negatively CD8+ T-cell exhaustion/dysfunction status. Insufficient activation resulting from alterations could not be attributed solely signaling. inhibited activity JAK2/STAT1 pathway by activating LYN/CD22/SH2 domain-containing phosphatase 1 (SHP1) axis, thereby limiting PDL1 IDO expression. Elevated CD58-deficient DLBCL led evasion tumor-intrinsic resistance chimeric antigen therapy. Direct CD58-CD2 costimulatory signaling combination anti-PDL1 blockade or inhibitor sensitized Collectively, work identified multiple roles responses Significance: Loss mediates upregulating LYN/CD22/SHP1 signaling, providing potential targets strategies improve patient treatment.

Language: Английский

Citations

6