Nature Cell Biology, Journal Year: 2020, Volume and Issue: 22(9), P. 1064 - 1075
Published: Aug. 24, 2020
Language: Английский
Nucleic Acids Research, Journal Year: 2020, Volume and Issue: 48(W1), P. W509 - W514
Published: May 17, 2020
Abstract Tumor progression and the efficacy of immunotherapy are strongly influenced by composition abundance immune cells in tumor microenvironment. Due to limitations direct measurement methods, computational algorithms often used infer cell from bulk transcriptome profiles. These estimated infiltrate populations have been associated with genomic transcriptomic changes tumors, providing insight into tumor–immune interactions. However, such investigations on large-scale public data remain challenging. To lower barriers for analysis complex interactions, we significantly improved our previous web platform TIMER. Instead just using one algorithm, TIMER2.0 (http://timer.cistrome.org/) provides more robust estimation infiltration levels The Cancer Genome Atlas (TCGA) or user-provided profiles six state-of-the-art algorithms. four modules investigating associations between infiltrates genetic clinical features, exploring cancer-related TCGA cohorts. Each module can generate a functional heatmap table, enabling user easily identify significant multiple cancer types simultaneously. Overall, server comprehensive visualization functions infiltrating cells.
Language: Английский
Citations
3778
Annals of Oncology, Journal Year: 2018, Volume and Issue: 30(1), P. 44 - 56
Published: Nov. 1, 2018
Treatment with immune checkpoint blockade (ICB) agents such as anti-programmed cell death protein 1 (PD-1), death-ligand (PD-L1), and/or anti-cytotoxic T-lymphocyte-associated 4 (CTLA-4) can result in impressive response rates and durable disease remission but only a subset of patients cancer. Expression PD-L1 has demonstrated utility selecting for to ICB proven be an important biomarker patient selection. Tumor mutation burden (TMB) is emerging potential biomarker. However, refinement interpretation contextualization required.
Language: Английский
Citations
2272
Journal of Cellular Physiology, Journal Year: 2018, Volume and Issue: 234(6), P. 8509 - 8521
Published: Nov. 22, 2018
CD8+ cytotoxic T lymphocytes (CTLs) are preferred immune cells for targeting cancer. During cancer progression, CTLs encounter dysfunction and exhaustion due to immunerelated tolerance immunosuppression within the tumor microenvironment (TME), with all favor adaptive immune-resistance. Cancer-associated fibroblasts (CAFs), macrophage type 2 (M2) cells, regulatory (Tregs) could make immunologic barriers against CD8 + cell-mediated antitumor responses. Thus, needed be primed activated toward effector in a process called immunity cycle making durable efficient The cell priming is directed essentially as corroboration work between of innate including dendritic (DCs) natural killer (NK) CD4 adoptive immunity. Upon activation, infiltrate core or invading site (so-called infiltrated-inflamed [I-I] TME) take essential roles killing cells. Exogenous reactivation and/or can possible using rational immunotherapy strategies. increase ratio costimulatory coinhibitory mediators checkpoint blockade (ICB) approach. Programmed death-1 receptor (PD-1)-ligand (PD-L1) CTL-associated antigen 4 (CTLA-4) receptors that targeted relieving renewing their priming, respectively, thereby eliminating antigen-expressing Due diverse relation Tregs, Treg activity dampened increasing number rescuing functional potential induce immunosensitivity
Language: Английский
Citations
1326
Journal of Hematology & Oncology, Journal Year: 2020, Volume and Issue: 13(1)
Published: Aug. 10, 2020
Abstract In recent years, cancer immunotherapy based on immune checkpoint inhibitors (ICIs) has achieved considerable success in the clinic. However, ICIs are significantly limited by fact that only one third of patients with most types respond to these agents. The induction cell death mechanisms other than apoptosis gradually emerged as a new treatment strategy because tumors harbor innate resistance apoptosis. date, possibility combining two modalities not been discussed systematically. Recently, few studies revealed crosstalk between distinct and antitumor immunity. pyroptosis, ferroptosis, necroptosis combined showed synergistically enhanced activity, even ICI-resistant tumors. Immunotherapy-activated CD8+ T cells traditionally believed induce tumor via following main pathways: (i) perforin-granzyme (ii) Fas-FasL. identified mechanism which suppress growth inducing ferroptosis provoked review relationship system activation. Hence, this review, we summarize knowledge reciprocal interaction immunity mechanisms, particularly necroptosis, three potentially novel immunogenic death. Because evidence is derived from using animal models, also reviewed related bioinformatics data available for human tissues public databases, partially confirmed presence interactions activation
Language: Английский
Citations
980
Nature Reviews Gastroenterology & Hepatology, Journal Year: 2021, Volume and Issue: 18(8), P. 525 - 543
Published: April 13, 2021
Hepatocellular carcinoma (HCC) is a prevalent disease with progression that modulated by the immune system. Systemic therapy used in advanced stage and until 2017 consisted only of antiangiogenic tyrosine kinase inhibitors (TKIs). Immunotherapy checkpoint has shown strong anti-tumour activity subset patients combination anti-PDL1 antibody atezolizumab VEGF-neutralizing bevacizumab or will soon become standard care as first-line for HCC, whereas anti-PD1 agents nivolumab pembrolizumab are after TKIs several regions. Other strategies such adoptive T-cell transfer, vaccination virotherapy have not yet demonstrated consistent clinical activity. Major unmet challenges HCC immunotherapy discovery validation predictive biomarkers, advancing treatment to earlier stages disease, applying liver dysfunction more effective combinatorial sequential approaches. Combinations other systemic local treatments perceived most promising opportunities some already under evaluation large-scale trials. This Review provides up-to-date information on best use currently available immunotherapies therapeutic development. Immunotherapeutic interventions might be tools hepatocellular carcinoma. carcinoma, mechanisms response resistance,
Language: Английский
Citations
951
Genome Medicine, Journal Year: 2020, Volume and Issue: 12(1)
Published: Feb. 26, 2020
Despite growing numbers of immune checkpoint blockade (ICB) trials with available omics data, it remains challenging to evaluate the robustness ICB response and evasion mechanisms comprehensively. To address these challenges, we integrated large-scale data biomarkers on published trials, non-immunotherapy tumor profiles, CRISPR screens a web platform TIDE (http://tide.dfci.harvard.edu). We processed for over 33K samples in 188 cohorts from public databases, 998 tumors 12 clinical studies, eight that identified gene modulators anticancer response. Integrating three interactive analysis modules, demonstrate utility reuse hypothesis generation, biomarker optimization, patient stratification.
Language: Английский
Citations
827
Nature, Journal Year: 2019, Volume and Issue: 567(7749), P. 479 - 485
Published: March 1, 2019
Language: Английский
Citations
785
Nature Medicine, Journal Year: 2019, Volume and Issue: 25(12), P. 1916 - 1927
Published: Dec. 1, 2019
Abstract Immune-checkpoint blockade (ICB) has demonstrated efficacy in many tumor types, but predictors of responsiveness to anti-PD1 ICB are incompletely characterized. In this study, we analyzed a clinically annotated cohort patients with melanoma ( n = 144) treated ICB, whole-exome and whole-transcriptome sequencing pre-treatment tumors. We found that mutational burden as predictor response was confounded by subtype, whereas multiple novel genomic transcriptomic features predicted selective response, including associated MHC-I MHC-II antigen presentation. Furthermore, previous anti-CTLA4 exposure different compared tumors were naive suggesting immune effects ICB. Finally, developed parsimonious models integrating clinical, predict intrinsic resistance individual tumors, validation smaller independent cohorts limited the availability comprehensive data. Broadly, present framework discover predictive build therapeutic response.
Language: Английский
Citations
784
Advanced Science, Journal Year: 2020, Volume and Issue: 7(7)
Published: Feb. 11, 2020
The distribution and abundance of immune cells, particularly T-cell subsets, play pivotal roles in cancer immunology therapy. T cells have many subsets with specific function current methods are limited estimating them, thus, a method for predicting comprehensive is urgently needed research. Here, Immune Cell Abundance Identifier (ImmuCellAI), gene set signature-based method, introduced precisely the 24 cell types including 18 from expression data. Performance evaluation on both sequencing data flow cytometry results public indicate that ImmuCellAI can estimate superior accuracy to other especially subsets. Application immunotherapy datasets reveals dendritic cytotoxic T, gamma delta significantly higher comparisons on-treatment versus pre-treatment responders non-responders. Meanwhile, an result-based model built response high (area under curve 0.80-0.91). These demonstrate powerful unique tumor infiltration estimation prediction.
Language: Английский
Citations
773
Nature reviews. Cancer, Journal Year: 2020, Volume and Issue: 20(4), P. 203 - 217
Published: March 11, 2020
Language: Английский
Citations
636