Determinants of anti-PD-1 response and resistance in clear cell renal cell carcinoma DOI Creative Commons
Lewis Au, Emine Hatipoglu, Marc Robert de Massy

et al.

Cancer Cell, Journal Year: 2021, Volume and Issue: 39(11), P. 1497 - 1518.e11

Published: Oct. 28, 2021

ADAPTeR is a prospective, phase II study of nivolumab (anti-PD-1) in 15 treatment-naive patients (115 multiregion tumor samples) with metastatic clear cell renal carcinoma (ccRCC) aiming to understand the mechanism underpinning therapeutic response. Genomic analyses show no correlation between molecular features and response, whereas ccRCC-specific human endogenous retrovirus expression indirectly correlates clinical T receptor (TCR) analysis reveals significantly higher number expanded TCR clones pre-treatment responders suggesting pre-existing immunity. Maintenance highly similar clusters TCRs post-treatment predict ongoing antigen engagement survival families cells likely recognizing same antigens. In responders, nivolumab-bound CD8

Language: Английский

The microbiome and human cancer DOI
Gregory D. Sepich‐Poore, Laurence Zitvogel, Ravid Straussman

et al.

Science, Journal Year: 2021, Volume and Issue: 371(6536)

Published: March 25, 2021

Microbial roles in cancer formation, diagnosis, prognosis, and treatment have been disputed for centuries. Recent studies provocatively claimed that bacteria, viruses, and/or fungi are pervasive among cancers, key actors immunotherapy, engineerable to treat metastases. Despite these findings, the number of microbes known directly cause carcinogenesis remains small. Critically evaluating building frameworks such evidence light modern biology is an important task. In this Review, we delineate between causal complicit trace common themes their influence through host's immune system, herein defined as immuno-oncology-microbiome axis. We further review intratumoral approaches manipulate gut or tumor microbiome while projecting next phase experimental discovery.

Language: Английский

Citations

895

Museum of spatial transcriptomics DOI Open Access
Lambda Moses, Lior Pachter

Nature Methods, Journal Year: 2022, Volume and Issue: 19(5), P. 534 - 546

Published: March 10, 2022

Language: Английский

Citations

734

Cell2location maps fine-grained cell types in spatial transcriptomics DOI
Vitalii Kleshchevnikov, Artem Shmatko, Emma Dann

et al.

Nature Biotechnology, Journal Year: 2022, Volume and Issue: 40(5), P. 661 - 671

Published: Jan. 13, 2022

Language: Английский

Citations

705

Integrating single-cell and spatial transcriptomics to elucidate intercellular tissue dynamics DOI
Sophia K. Longo, Margaret Guo, Andrew L. Ji

et al.

Nature Reviews Genetics, Journal Year: 2021, Volume and Issue: 22(10), P. 627 - 644

Published: June 18, 2021

Language: Английский

Citations

675

Methods and applications for single-cell and spatial multi-omics DOI Open Access
Katy Vandereyken, Alejandro Sifrim, Bernard Thienpont

et al.

Nature Reviews Genetics, Journal Year: 2023, Volume and Issue: 24(8), P. 494 - 515

Published: March 2, 2023

Language: Английский

Citations

626

Overview of multiplex immunohistochemistry/immunofluorescence techniques in the era of cancer immunotherapy DOI Creative Commons

Wei Tan,

Sanjna Nilesh Nerurkar,

Hai Yun Cai

et al.

Cancer Communications, Journal Year: 2020, Volume and Issue: 40(4), P. 135 - 153

Published: April 1, 2020

Abstract Conventional immunohistochemistry (IHC) is a widely used diagnostic technique in tissue pathology. However, this associated with number of limitations, including high inter‐observer variability and the capacity to label only one marker per section. This review details various highly multiplexed techniques that have emerged circumvent these constraints, allowing simultaneous detection multiple markers on single section comprehensive study cell composition, cellular functional cell‐cell interactions. Among techniques, multiplex Immunohistochemistry/Immunofluorescence (mIHC/IF) has be particularly promising. mIHC/IF provides high‐throughput staining standardized quantitative analysis for reproducible, efficient cost‐effective studies. immediate potential translational research clinical practice, era cancer immunotherapy.

Language: Английский

Citations

492

An introduction to spatial transcriptomics for biomedical research DOI Creative Commons

Cameron G. Williams,

Hyun Jae Lee,

Takahiro Asatsuma

et al.

Genome Medicine, Journal Year: 2022, Volume and Issue: 14(1)

Published: June 27, 2022

Abstract Single-cell transcriptomics (scRNA-seq) has become essential for biomedical research over the past decade, particularly in developmental biology, cancer, immunology, and neuroscience. Most commercially available scRNA-seq protocols require cells to be recovered intact viable from tissue. This precluded many cell types study largely destroys spatial context that could otherwise inform analyses of identity function. An increasing number platforms now facilitate spatially resolved, high-dimensional assessment gene transcription, known as ‘spatial transcriptomics’. Here, we introduce different classes method, which either record locations hybridized mRNA molecules tissue, image positions themselves prior assessment, or employ arrays probes pre-determined location. We review sizes tissue area can assessed, their resolution, genes profiled. discuss if preservation influences choice platform, provide guidance on whether specific may better suited discovery screens hypothesis testing. Finally, bioinformatic methods analysing transcriptomic data, including pre-processing, integration with existing inference cell-cell interactions. Spatial -omics are already improving our understanding human tissues research, diagnostic, therapeutic settings. To build upon these recent advancements, entry-level those seeking own research.

Language: Английский

Citations

467

Effect of the intratumoral microbiota on spatial and cellular heterogeneity in cancer DOI Creative Commons
Jorge Luis Galeano Niño, Hanrui Wu, Kaitlyn D. LaCourse

et al.

Nature, Journal Year: 2022, Volume and Issue: 611(7937), P. 810 - 817

Published: Nov. 16, 2022

Abstract The tumour-associated microbiota is an intrinsic component of the tumour microenvironment across human cancer types 1,2 . Intratumoral host–microbiota studies have so far largely relied on bulk tissue analysis 1–3 , which obscures spatial distribution and localized effect within tumours. Here, by applying in situ spatial-profiling technologies 4 single-cell RNA sequencing 5 to oral squamous cell carcinoma colorectal cancer, we reveal spatial, cellular molecular host–microbe interactions. We adapted 10x Visium transcriptomics determine identity location intratumoral microbial communities patient tissues. Using GeoMx digital profiling 6 show that bacterial populate microniches are less vascularized, highly immuno‑suppressive associated with malignant cells lower levels Ki-67 as compared bacteria-negative regions. developed a RNA-sequencing method name INVADEseq (invasion–adhesion-directed expression sequencing) and, this tumours, identify cell-associated bacteria host they interact, well uncovering alterations transcriptional pathways involved inflammation, metastasis, dormancy DNA repair. Through functional studies, infected invade their surrounding environment single recruit myeloid Collectively, our data not random; instead, it organized immune epithelial functions promote progression.

Language: Английский

Citations

462

The technological landscape and applications of single-cell multi-omics DOI Open Access
Alev Baysoy, Zhiliang Bai, Rahul Satija

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2023, Volume and Issue: 24(10), P. 695 - 713

Published: June 6, 2023

Language: Английский

Citations

461

High-plex imaging of RNA and proteins at subcellular resolution in fixed tissue by spatial molecular imaging DOI
Shanshan He,

Ruchir Bhatt,

Carl Brown

et al.

Nature Biotechnology, Journal Year: 2022, Volume and Issue: 40(12), P. 1794 - 1806

Published: Oct. 6, 2022

Language: Английский

Citations

416