B cells and tertiary lymphoid structures as determinants of tumour immune contexture and clinical outcome

Nature Reviews Clinical Oncology, Journal Year: 2022, Volume and Issue: 19(7), P. 441 - 457

Published: April 1, 2022

Language: Английский

---

The cancer-immunity cycle: Indication, genotype, and immunotype

Immunity, Journal Year: 2023, Volume and Issue: 56(10), P. 2188 - 2205

Published: Oct. 1, 2023

The cancer-immunity cycle provides a framework to understand the series of events that generate anti-cancer immune responses. It emphasizes iterative nature response where killing tumor cells by T initiates subsequent rounds antigen presentation and cell stimulation, maintaining active immunity adapting it evolution. Any step can become rate-limiting, rendering system unable control growth. Here, we update based on remarkable progress past decade. Understanding mechanism checkpoint inhibition has evolved, as our view dendritic in sustaining anti-tumor immunity. We additionally account for role microenvironment facilitating, not just suppressing, response, discuss importance considering tumor's immunological phenotype, "immunotype". While these new insights add some complexity cycle, they also provide targets research therapeutic intervention.

Language: Английский

---

High-resolution single-cell atlas reveals diversity and plasticity of tissue-resident neutrophils in non-small cell lung cancer

Cancer Cell, Journal Year: 2022, Volume and Issue: 40(12), P. 1503 - 1520.e8

Published: Nov. 10, 2022

Non-small cell lung cancer (NSCLC) is characterized by molecular heterogeneity with diverse immune infiltration patterns, which has been linked to therapy sensitivity and resistance. However, full understanding of how phenotypes vary across different patient subgroups lacking. Here, we dissect the NSCLC tumor microenvironment at high resolution integrating 1,283,972 single cells from 556 samples 318 patients 29 datasets, including our dataset capturing low mRNA content. We stratify into immune-deserted, B cell, T myeloid subtypes. Using bulk genomic clinical information, identify cellular components associated histology genotypes. then focus on analysis tissue-resident neutrophils (TRNs) uncover distinct subpopulations that acquire new functional properties in tissue microenvironment, providing evidence for plasticity TRNs. Finally, show a TRN-derived gene signature anti-programmed death ligand 1 (PD-L1) treatment failure.

Language: Английский

---

Intratumoral dendritic cell–CD4+ T helper cell niches enable CD8+ T cell differentiation following PD-1 blockade in hepatocellular carcinoma

Nature Medicine, Journal Year: 2023, Volume and Issue: 29(6), P. 1389 - 1399

Published: June 1, 2023

Language: Английский

---

Antibodies against endogenous retroviruses promote lung cancer immunotherapy

Nature, Journal Year: 2023, Volume and Issue: 616(7957), P. 563 - 573

Published: April 12, 2023

Abstract B cells are frequently found in the margins of solid tumours as organized follicles ectopic lymphoid organs called tertiary structures (TLS) 1,2 . Although TLS have been to correlate with improved patient survival and response immune checkpoint blockade (ICB), underlying mechanisms this association remain elusive Here we investigate lung-resident cell responses patients from TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) other lung cancer cohorts, a recently established immunogenic mouse model for adenocarcinoma 3 We find that both human adenocarcinomas elicit local germinal centre tumour-binding antibodies, further identify endogenous retrovirus (ERV) envelope glycoproteins dominant anti-tumour antibody target. ERV-targeting amplified by ICB humans mice, targeted inhibition KRAS(G12C) model. ERV-reactive antibodies exert activity extends model, ERV expression predicts outcome adenocarcinoma. Finally, effective immunotherapy requires CXCL13-dependent formation. Conversely, therapeutic CXCL13 treatment potentiates immunity synergizes ICB. Our findings provide possible mechanistic basis response.

Language: Английский

---

Neoadjuvant chemotherapy plus nivolumab with or without ipilimumab in operable non-small cell lung cancer: the phase 2 platform NEOSTAR trial

Nature Medicine, Journal Year: 2023, Volume and Issue: 29(3), P. 593 - 604

Published: March 1, 2023

Abstract Neoadjuvant ipilimumab + nivolumab (Ipi+Nivo) and chemotherapy (Nivo+CT) induce greater pathologic response rates than CT alone in patients with operable non-small cell lung cancer (NSCLC). The impact of adding to neoadjuvant Nivo+CT is unknown. Here we report the results correlates two arms phase 2 platform NEOSTAR trial testing Ipi+Nivo+CT major (MPR) as primary endpoint. MPR were 32.1% (7/22, 80% confidence interval (CI) 18.7–43.1%) arm 50% (11/22, CI 34.6–61.1%) arm; endpoint was met both arms. In without known tumor EGFR / ALK alterations, 41.2% (7/17) 62.5% (10/16) groups, respectively. No new safety signals observed either arm. Single-cell sequencing multi-platform immune profiling (exploratory endpoints) underscored populations phenotypes, including effector memory CD8 T, B myeloid cells markers tertiary lymphoid structures, that preferentially increased cohort. Baseline fecal microbiota enriched beneficial taxa, such Akkermansia , displayed reduced abundance pro-inflammatory pathogenic microbes. enhances responses warrants further study NSCLC. (ClinicalTrials.gov registration: NCT03158129 .)

Language: Английский

---

Dissecting the treatment-naive ecosystem of human melanoma brain metastasis

Cell, Journal Year: 2022, Volume and Issue: 185(14), P. 2591 - 2608.e30

Published: July 1, 2022

Language: Английский

---

Tertiary lymphoid structures and B cells: An intratumoral immunity cycle

Immunity, Journal Year: 2023, Volume and Issue: 56(10), P. 2254 - 2269

Published: Sept. 11, 2023

Language: Английский

---

The heterogeneous immune landscape between lung adenocarcinoma and squamous carcinoma revealed by single-cell RNA sequencing

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Aug. 26, 2022

Abstract A thorough interrogation of the immune landscape is crucial for immunotherapy strategy selection and prediction clinical responses in non-small-cell lung cancer (NSCLC) patients. Single-cell RNA sequencing (scRNA-seq) techniques have prompted opportunity to dissect distinct signatures between adenocarcinoma (LUAD) squamous cell carcinoma (LUSC), two major subtypes NSCLC. Here, we performed scRNA-seq on 72,475 cells from 40 samples tumor matched adjacent normal tissues spanning 19 NSCLC patients, drew a systematic transcriptome atlas. Joint analyses cellular compositions, differentially expressed genes (DEGs), cell–cell interactions, pseudotime trajectory, transcriptomic factors prognostic based The Cancer Genome Atlas (TCGA), revealed central roles cytotoxic effector T NK functional macrophages (Mφ) microenvironment heterogeneity LUAD LUSC. dominant subtype Mφ was FABP4- SPP1- Importantly, identified novel lymphocyte-related cluster, which named SELENOP- Mφ, further established its antitumor role both types, especially LUAD. Our comprehensive depiction definition clusters could help design personalized treatment patients practice.

Language: Английский

---

Microwave Radiation and the Brain: Mechanisms, Current Status, and Future Prospects

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(16), P. 9288 - 9288

Published: Aug. 18, 2022

Modern humanity wades daily through various radiations, resulting in frequent exposure and causing potentially important biological effects. Among them, the brain is organ most sensitive to electromagnetic radiation (EMR) exposure. Despite numerous correlated studies, critical unknowns surround different parameters used, including operational frequency, power density (i.e., energy dose), irradiation time that could permit reproducibility comparability between analyses. Furthermore, interactions of EMR with systems its precise mechanisms remain poorly characterized. In this review, recent approaches examining effects microwave radiations on brain, specifically learning memory capabilities, as well dysfunction reported literature, are analyzed interpreted provide prospective views for future research directed at novel medical technology developing preventive therapeutic strategies degeneration caused by radiation. Additionally, microwaves possible presented review. Treatment natural products safe techniques reduce harm organs have become essential components life, some promising treat cancers their radioprotective summarized well. This review can serve a platform researchers understand mechanism systems, present scenario, prospects studies effect brain.

Language: Английский

---