Pan-cancer and experimental analyses reveal the immunotherapeutic significance of CST2 and its association with stomach adenocarcinoma proliferation and metastasis DOI Creative Commons
Dan Huang, Jing Li,

Zhijun He

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 24, 2025

Purpose Cystatin 2 (CST2) is a cysteine protease inhibitor, and recent research suggests its potential involvement in cancer development. However, role the occurrence, progression, prognosis of pan-cancer has not been systematically investigated. Materials methods This study comprehensively analyzes differential expression CST2 pan-cancer. The distribution patterns were examined using single-cell datasets. Furthermore, we conducted comprehensive evaluation correlation between various factors. These factors include prognosis, immune cell infiltration, immune-related genes, mutations, methylation, tumor mutation burden (TMB), microsatellite instability (MSI). In addition, analyzed sensitivity drugs dependent on expression. We utilized gene set enrichment analysis (GSEA) to explore biological functions across different types. Finally, gastric lines, will investigate impact knockout levels, clonal proliferation, apoptosis, migration. Results exhibits abnormal overexpression multiple tumors. Single-cell reveals high fibroblasts. closely associated with TMB, MSI. Enrichment demonstrated significant pathways. stomach adenocarcinoma (STAD), CST2-related risk models are demonstrate strong predictive capabilities, while also being linked microenvironment. Drug indicates 21 chemotherapy drugs. experimental validation revealed significantly elevated STAD, indicating as driver regulating malignant proliferation Conclusion serves biomarker, playing critical facilitating migration processes STAD.

Language: Английский

The evolving tumor microenvironment: From cancer initiation to metastatic outgrowth DOI Creative Commons
Karin E. de Visser, Johanna A. Joyce

Cancer Cell, Journal Year: 2023, Volume and Issue: 41(3), P. 374 - 403

Published: March 1, 2023

Language: Английский

Citations

1539
Antibodies against endogenous retroviruses promote lung cancer immunotherapy DOI Creative Commons
Kevin W. Ng, Jesse Boumelha, Katey S.S. Enfield

et al.

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

Citations

157
Tertiary lymphoid structures and B cells: An intratumoral immunity cycle DOI Creative Commons
Wolf H. Fridman, Maxime Meylan, Guilhem Pupier

et al.

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

Published: Sept. 11, 2023

Language: Английский

Citations

116
The roles of ferroptosis in cancer: Tumor suppression, tumor microenvironment, and therapeutic interventions DOI Open Access
Guang Lei, Li Zhuang, Boyi Gan

et al.

Cancer Cell, Journal Year: 2024, Volume and Issue: 42(4), P. 513 - 534

Published: April 1, 2024

Language: Английский

Citations

116
T follicular helper cells in cancer DOI Creative Commons
Nicolás Gutiérrez-Melo, Dirk Baumjohann

Trends in cancer, Journal Year: 2023, Volume and Issue: 9(4), P. 309 - 325

Published: Jan. 14, 2023

T follicular helper (Tfh) cells provide essential help to B for effective antibody-mediated immune responses. Although the crucial function of these CD4+ in infection and vaccination is well established, their involvement cancer only beginning emerge. Increased numbers Tfh cell-derived or cell-associated malignancies are often associated with an unfavorable outcome, whereas various solid organ tumor types non-lymphocytic origin, presence frequently coincides a better prognosis. We discuss recent advances understanding how cell crosstalk CD8+ secondary tertiary lymphoid structures (TLS) enhances antitumor immunity, but may also exacerbate immune-related adverse events (irAEs) such as autoimmunity during checkpoint blockade (ICB) immunotherapy.

Language: Английский

Citations

105
CT Radiomics to Predict Macrotrabecular-Massive Subtype and Immune Status in Hepatocellular Carcinoma DOI
Zhichao Feng, Huiling Li, Qianyun Liu

et al.

Radiology, Journal Year: 2022, Volume and Issue: 307(1)

Published: Dec. 13, 2022

Background Macrotrabecular-massive (MTM) subtype of hepatocellular carcinoma (HCC) is an aggressive variant associated with angiogenesis and immunosuppressive tumor microenvironment, which expected to be noninvasively identified using radiomics approaches. Purpose To construct a CT model predict the MTM investigate underlying immune infiltration patterns. Materials Methods This study included five retrospective data sets one prospective set from three academic medical centers between January 2015 December 2021. The preoperative liver contrast-enhanced studies 365 adult patients resected HCC were evaluated. Third Xiangya Hospital Central South University provided training internal test set, while Yueyang Hunan Cancer external sets. Radiomic features extracted used develop machine learning in performance was verified two outcomes cohort, including 58 advanced undergoing transarterial chemoembolization antiangiogenic therapy, evaluate predictive value for progression-free survival (PFS). Bulk RNA sequencing tumors 41 Genome Atlas (TCGA) single-cell seven prospectively enrolled participants radiomics-related Area under receiver operating characteristics curve calculated, Cox proportional regression performed identify predictors PFS. Results Among (mean age, 55 years ± 10 [SD]; 319 men) modeling, 122 (33%) confirmed have subtype. 11 radiomic showed good predicting subtype, AUCs 0.84, 0.80, 0.74 respectively. A low score relative median cohort independently PFS (hazard ratio, 0.4; 95% CI: 0.2, 0.8; P = .01). dysregulated humoral immunity involving B-cell immunoglobulin synthesis. Conclusion Accurate prediction macrotrabecular-massive achieved model, also defective immunity. Published CC BY 4.0 license. Supplemental material available this article. See editorial by Yoon Kim issue.

Language: Английский

Citations

92
B cells in the tumor microenvironment: Multi-faceted organizers, regulators, and effectors of anti-tumor immunity DOI Creative Commons
Céline M. Laumont, Brad H. Nelson

Cancer Cell, Journal Year: 2023, Volume and Issue: 41(3), P. 466 - 489

Published: March 1, 2023

Language: Английский

Citations

92
Predictive biomarkers of colon cancer immunotherapy: Present and future DOI Creative Commons

Wanting Hou,

Yi Cheng, Hong Zhu

et al.

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Nov. 22, 2022

Immunotherapy has revolutionized colon cancer treatment. Immune checkpoint inhibitors (ICIs) have shown clinical benefits for patients, especially those with high microsatellite instability (MSI-H). In 2020, the US Food and Drug Administration (FDA)-approved ICI pembrolizumab as first-line treatment metastatic MSI-H patients. Additionally, neoadjuvant immunotherapy presented efficacy in treating early-stage Although MSI been thought of an effective predictive biomarker immunotherapy, only a small proportion patients were MSI-H, certain intrinsic or acquired resistance to immunotherapy. Thus, further search biomarkers stratify is meaningful Except MSI, other biomarkers, such PD-L1 expression level, tumor mutation burden (TMB), tumor-infiltrating lymphocytes (TILs), gut microbiota, ctDNA, circulating immune cells also proposed be correlated patient survival some studies. Moreover, developing new diagnostic techniques helps identify accurate this review, we outline reported discuss prospects technological changes development

Language: Английский

Citations

90
Radiation-induced tumor immune microenvironments and potential targets for combination therapy DOI Creative Commons
Siyu Guo, Yihan Yao,

Yang Tang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: May 19, 2023

As one of the four major means cancer treatment including surgery, radiotherapy (RT), chemotherapy, immunotherapy, RT can be applied to various cancers as both a radical and an adjuvant before or after surgery. Although is important modality for treatment, consequential changes caused by in tumor microenvironment (TME) have not yet been fully elucidated. RT-induced damage cells leads different outcomes, such survival, senescence, death. During RT, alterations signaling pathways result local immune microenvironment. However, some are immunosuppressive transform into phenotypes under specific conditions, leading development radioresistance. Patients who radioresistant respond poorly may experience progression. Given that emergence radioresistance inevitable, new radiosensitization treatments urgently needed. In this review, we discuss irradiated TME regimens describe existing potential molecules could targeted improve therapeutic effects RT. Overall, review highlights possibilities synergistic therapy building on research.

Language: Английский

Citations

69
A blueprint for tumor-infiltrating B cells across human cancers DOI
Jiaqiang Ma, Yingcheng Wu, Lifeng Ma

et al.

Science, Journal Year: 2024, Volume and Issue: 384(6695)

Published: May 2, 2024

B lymphocytes are essential mediators of humoral immunity and play multiple roles in human cancer. To decode the functions tumor-infiltrating cells, we generated a cell blueprint encompassing single-cell transcriptome, cell-receptor repertoire, chromatin accessibility data across 20 different cancer types (477 samples, 269 patients). cells harbored extraordinary heterogeneity comprised 15 subsets, which could be grouped into two independent developmental paths (extrafollicular versus germinal center). Tumor extrafollicular pathway were linked with worse clinical outcomes resistance to immunotherapy. The dysfunctional program was associated glutamine-derived metabolites through epigenetic-metabolic cross-talk, promoted T cell-driven immunosuppressive program. These suggest an intratumor balance between germinal-center responses that possibly harnessed for cell-targeting

Language: Английский

Citations

66