BCAT2 Shapes a Noninflamed Tumor Microenvironment and Induces Resistance to Anti‐PD‐1/PD‐L1 Immunotherapy by Negatively Regulating Proinflammatory Chemokines and Anticancer Immunity

Cai, Zhiyong; Chen, Jinbo; Yu, Zheng-Zheng; Li, Huihuang; Li, Zhi; Deng, Dingshan; Liu, Jinhui; Chen, Chunliang; Zhang, Chunyu; Ou, Zhenyu; Chen, Minfeng; Hu, Jiao; Zu, Xiongbing

doi:10.1002/advs.202207155

Cited by 27 publications

(20 citation statements)

References 92 publications

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“…Genes expressed in tumor tissues, especially immune gene pro les, can regulate the function, in ltration, and phenotypes of various immune cells in the tumor microenvironment. Several studies have analyzed the immune tumor microenvironment by gene expression pro ling in the search of predictive bio-markers, such as BCAT2 shapes a nonin amed TIME by inhibiting activities of cytokine/chemokine related pathways ,or TSC1/2 is involved in maintaining T cell activation [29][30][31][32][33]. Environmental factors can in uence epigenetic processes, change gene expression, and have a great impact on tumor progression and metastasis.…”

Section: Discussionmentioning

confidence: 99%

The Impact of Heterogeneity on the Effectiveness of Immune Checkpoint Inhibitors: A Case Series on Metastatic Urothelial Carcinoma

Zhao,

Zhou,

Wan

et al. 2024

Preprint

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Purpose: To investigate the disparities in tumor parenchyma and microenvironment between primary tumors and metastasis of urothelial carcinoma. Additionally, the study aims to determine whether the heterogeneity in these factors affects the predictive effectiveness of immune checkpoint inhibitors. Methods: In this retrospective study, we investigated the treatment outcomes of 5 patients with metastatic urothelial carcinoma who were treated with first-line immune checkpoint inhibitors. We analyzed various biomarkers including genomic profile, programmed cell death receptor ligand-1 expression, tumor mutation burden, microsatellite instability, T-cell ratio, and tertiary lymphoid structure in both primary and metastatic samples. Additionally, we collected and analyzed relevant clinical data. Results: At the genetic level, the main different genes were TSC1/2, MCL1, RAC1. TSC1/2 and MCL1 were acquired by metastases and RAC1 were lost by metastases. There were differences in programmed cell death receptor ligand-1, tumor mutation burden, T-cell ratio, tertiary lymphoid structure . All tumors in this study were microsatellite stable. In two patients with clinical disease control, the proportion of CD3+ T cell and CD8+ T cell in metastases increased compared with the primary tumors, and tertiary lymphatic structure changed from negative to positive expression. These results suggest that metastases may have more lymphocytic infiltrates and some form tertiary lymphoid structures, and patients with this feature may respond better to immune checkpoint inhibitors. Conclusions: The analysis revealed both similarities and differences between primary and distant metastasis samples in the context of urothelial carcinoma. We strongly advocate for re-biopsy of metastases following the occurrence of metastases and suggest that treatment methods should be chosen based on the detection of these metastases.

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Section: Discussionmentioning

confidence: 99%

The Impact of Heterogeneity on the Effectiveness of Immune Checkpoint Inhibitors: A Case Series on Metastatic Urothelial Carcinoma

Zhao,

Zhou,

Wan

et al. 2024

Preprint

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“…Cai et al. ( 35 ) and Hu et al. ( 36 ) revealed the critical significance of BCAT2 and Siglec15 in the tumor microenvironment of BLCA patients.…”

Section: Discussionmentioning

confidence: 99%

Identification of FLRT2 as a key prognostic gene through a comprehensive analysis of TMB and IRGPs in BLCA patients

Tao,

Yu,

Cong

et al. 2024

Front. Oncol.

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IntroductionThe tumor immune environment and immune-related genes are instrumental in the development, progression, and prognosis of bladder cancer (BLCA). This study sought to pinpoint key immune-related genes influencing BLCA prognosis and decipher their mechanisms of action.Methods and resultsWe analyzed differentially expressed genes (DEGs) between high- and low- tumor mutational burden (TMB) groups. Subsequently, we constructed a reliable prognostic model based on immune-related gene pairs (IRGPs) and analyzed DEGs between high- and low-risk groups. A total of 22 shared DEGs were identified across differential TMB and IRGPs-derived risk groups in BLCA patients. Through univariate Cox and multivariate Cox analyses, we highlighted five genes - FLRT2, NTRK2, CYTL1, ZNF683, PRSS41 - significantly correlated with BLCA patient prognosis. Notably, the FLRT2 gene emerged as an independent prognostic factor for BLCA, impacting patient prognosis via modulation of macrophage infiltration in immune microenvironment. Further investigation spotlighted methylation sites - cg25120290, cg02305242, and cg01832662 - as key regulators of FLRT2 expression.DiscussionThese findings identified pivotal prognostic genes in BLCA and illuminated the intricate mechanisms dictating patient prognosis. This study not only presents a novel prognostic marker but also carves out potential avenues for immunotherapy and targeted therapeutic strategies in BLCA. By demystifying the profound impact of immune-related genes and the tumor immune environment, this study augments the comprehension and prognostic management of bladder cancer.

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“…Ji et al 50 found that for NMIBC patients, rapamycin enhances BCG-specific gamma delta T cell immunity and boosts urinary cytokines during BCG treatment. Recent, Li et al 51 and Cai et al 52 successively reported that S100A5 and BCAT2 can shape a non-inflamed TME in BC by negatively regulating pro-inflammatory chemokines and the recruitment and cytotoxicity of CD8 T cells. S100A5 and BCAT2, as key molecules in TME, are emerging targets in combination with ICB, which can enhance the efficacy of ICB therapy in BC.…”

Section: Research Hotspots and Frontiersmentioning

confidence: 99%

Knowledge-map analysis of bladder cancer immunotherapy

Lv,

Hou,

Wang

et al. 2023

Human Vaccines & Immunotherapeutics

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This study aimed to conduct a bibliometric analysis in the field of bladder cancer (BC) immunotherapy, and explore the research trends, hotspots and frontiers from 2000 to 2022. VOSviewer software was used to analyze the collaborative relationships between authors, institutions, countries/regions, and journals through citation, co-authorship, and co-citation analysis, to identify research hotspots and frontiers in this field. Researchers based in the United States of America have published a total of 627 papers with 27,308 citations. Indeed, the USA ranked first among the top 10 most active countries and showed the most extensive collaboration with other countries. The University of Texas MD Anderson CANC CTR has published 58 articles, making it the top most institution in terms of published articles and active collaborative research. Kamat AM and Lamm DL were the most active and co-cited authors with 28 papers and 980 co-citations, respectively. Chang Yuan and Xu le were the most active collaborative authors with a total link strength of 195. The J UROLOGY was the most active and frequently co-cited journal, with 100 papers and 6,668 co-citations. Studies of BC immunotherapy can be broadly classified into three categories: “basic research”, “clinical trial”, and “prognosis”. Our findings provide an overview of the research priorities and future directions of BC immunotherapy. Tumor microenvironment and immune checkpoint inhibitors (ICIs) of BC, as well as the combination of ICIs with other drugs, may become the main direction of future research.

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BCAT2 Shapes a Noninflamed Tumor Microenvironment and Induces Resistance to Anti‐PD‐1/PD‐L1 Immunotherapy by Negatively Regulating Proinflammatory Chemokines and Anticancer Immunity

Cited by 27 publications

References 92 publications

The Impact of Heterogeneity on the Effectiveness of Immune Checkpoint Inhibitors: A Case Series on Metastatic Urothelial Carcinoma

The Impact of Heterogeneity on the Effectiveness of Immune Checkpoint Inhibitors: A Case Series on Metastatic Urothelial Carcinoma

Identification of FLRT2 as a key prognostic gene through a comprehensive analysis of TMB and IRGPs in BLCA patients

Knowledge-map analysis of bladder cancer immunotherapy

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