Immunotherapies for hepatocellular carcinoma

Nature Reviews Clinical Oncology, Journal Year: 2021, Volume and Issue: 19(3), P. 151 - 172

Published: Nov. 11, 2021

Language: Английский

---

Treatment landscape of triple-negative breast cancer — expanded options, evolving needs

Nature Reviews Clinical Oncology, Journal Year: 2021, Volume and Issue: 19(2), P. 91 - 113

Published: Nov. 9, 2021

Language: Английский

---

The Next Decade of Immune Checkpoint Therapy

Cancer Discovery, Journal Year: 2021, Volume and Issue: 11(4), P. 838 - 857

Published: April 1, 2021

Immune checkpoint therapy (ICT) can provide durable clinical responses and improve overall survival. However, only subsets of patients with specific tumor types respond to ICT. Thus, significant challenges remain, including understanding pathways resistance, optimizing patient selection, improving management immune-related adverse events, identifying rational therapeutic combinations. These will need a focused approach encompassing both basic research, the integration reverse translational studies. This integrated lead identification potential targets for subsequent trials, which guide decisions as we develop novel combination strategies maximize efficacy minimize toxicities patients. SIGNIFICANCE: ICTs induce antitumor cancer. Recent evidence suggests that combinatorial response by overcoming primary adaptive resistance mechanisms, although these may carry an increased risk immune-mediated toxicities. review surveys current mechanisms active areas investigation, proposes path forward minimizing through better selection

Language: Английский

---

Spatially organized multicellular immune hubs in human colorectal cancer

Cell, Journal Year: 2021, Volume and Issue: 184(18), P. 4734 - 4752.e20

Published: Aug. 26, 2021

Immune responses to cancer are highly variable, with mismatch repair-deficient (MMRd) tumors exhibiting more anti-tumor immunity than repair-proficient (MMRp) tumors. To understand the rules governing these varied responses, we transcriptionally profiled 371,223 cells from colorectal and adjacent normal tissues of 28 MMRp 34 MMRd individuals. Analysis 88 cell subsets their 204 associated gene expression programs revealed extensive transcriptional spatial remodeling across discover hubs interacting malignant immune cells, identified in different types that co-varied affected individuals used profiling localize coordinated programs. We discovered a myeloid cell-attracting hub at tumor-luminal interface tissue damage an MMRd-enriched within tumor, activated T together expressing chemokines. By identifying cellular programs, reveal logic underlying spatially organized immune-malignant networks.

Language: Английский

---

Artificial Intelligence in Cancer Research and Precision Medicine

Cancer Discovery, Journal Year: 2021, Volume and Issue: 11(4), P. 900 - 915

Published: April 1, 2021

Artificial intelligence (AI) is rapidly reshaping cancer research and personalized clinical care. Availability of high-dimensionality datasets coupled with advances in high-performance computing, as well innovative deep learning architectures, has led to an explosion AI use various aspects oncology research. These applications range from detection classification cancer, molecular characterization tumors their microenvironment, drug discovery repurposing, predicting treatment outcomes for patients. As these start penetrating the clinic, we foresee a shifting paradigm care becoming strongly driven by AI. SIGNIFICANCE: potential dramatically affect nearly all oncology-from enhancing diagnosis personalizing discovering novel anticancer drugs. Here, review recent enormous progress application oncology, highlight limitations pitfalls, chart path adoption clinic.

Language: Английский

---

Targeting CDK4 and CDK6 in cancer

Nature reviews. Cancer, Journal Year: 2022, Volume and Issue: 22(6), P. 356 - 372

Published: March 18, 2022

Language: Английский

---

Turning cold tumors hot: from molecular mechanisms to clinical applications

Trends in Immunology, Journal Year: 2022, Volume and Issue: 43(7), P. 523 - 545

Published: May 25, 2022

Language: Английский

---

Molecular signatures of antitumor neoantigen-reactive T cells from metastatic human cancers

Science, Journal Year: 2022, Volume and Issue: 375(6583), P. 877 - 884

Published: Feb. 24, 2022

The accurate identification of antitumor T cell receptors (TCRs) represents a major challenge for the engineering cell-based cancer immunotherapies. By mapping 55 neoantigen-specific TCR clonotypes (NeoTCRs) from 10 metastatic human tumors to their single-cell transcriptomes, we identified signatures CD8

Language: Английский

---

Dynamics and specificities of T cells in cancer immunotherapy

Nature reviews. Cancer, Journal Year: 2023, Volume and Issue: 23(5), P. 295 - 316

Published: April 12, 2023

Language: Английский

---

Real-world application of tumor mutational burden-high (TMB-high) and microsatellite instability (MSI) confirms their utility as immunotherapy biomarkers

ESMO Open, Journal Year: 2021, Volume and Issue: 7(1), P. 100336 - 100336

Published: Dec. 23, 2021

Microsatellite instability (MSI) testing and tumor mutational burden (TMB) are genomic biomarkers used to identify patients who likely benefit from immune checkpoint inhibitors. Pembrolizumab was recently approved by the Food Drug Administration for use in TMB-high (TMB-H) tumors, regardless of histology, based on KEYNOTE-158. The primary objective this retrospective study real-world applicability immunotherapy TMB/MSI-high lend credence refine biomarker.Charts with advanced solid tumors had MSI/TMB status determined next generation sequencing (NGS) (FoundationOne CDx) were reviewed. Demographics, diagnosis, treatment history, overall response rate (ORR) abstracted. Progression-free survival (PFS) Kaplan-Meier curves. PFS1 (chemotherapy PFS) PFS2 (immunotherapy received after progressing chemotherapy. median PFS2/PFS1 ratio recorded.MSI-high or TMB-H [≥20 mutations per megabase (mut/MB)] detected 157 adults a total 27 distinct histologies. Median turnaround time NGS 73 days. ORR most recent chemotherapy 34.4%. 55.9%. PFS versus 6.75 months (95% confidence interval, 3.9-10.9 months) 24.2 9.6 not reached), respectively (P = 0.042). 4.7 favor immunotherapy.This reinforces TMB as predictive biomarker. Barriers exist timely implementation NGS-based more data needed raise awareness about clinical utility TMB. Clinicians should consider treating their histology.

Language: Английский

---