CHMP2A regulates tumor sensitivity to natural killer cell-mediated cytotoxicity

Bernareggi, Davide; Xie, Qi; Prager, Briana C.; Yun, Ji-Young; Cruz, Luisjesus S.; Pham, Timothy V.; Kim, William; Lee, Xiqing; Coffey, Michael; Zalfa, Cristina; Azmoon, Pardis; Huang, Zhu; Tamayo, Pablo; Rich, Jeremy; Kaufman, Dan S.

doi:10.1038/s41467-022-29469-0

Cited by 35 publications

(39 citation statements)

References 78 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, the PRG prognostic signature incorporating these two genes could be used to stratify LUAD patients into different risk groups and guide individualized treatment decisions. Previous literature identified that it has been proposed that CHMP2A, a subunit of endosomal sorting complexes required for transport III (ESCRT-III), may help enhance the effect of NK cells on tumor cells ( Bernareggi et al, 2022 ). The data demonstrates that CHMP2A and extracellular vesicles released by tumors can induce programmed cell death in NK cells, thereby diminishing their capacity to efficiently eliminate cancer cells.…”

Section: Discussionmentioning

confidence: 99%

A novel pyroptosis-related prognostic signature for lung adenocarcinoma: Identification and multi-angle verification

Wang

Zhou

et al. 2023

Front. Genet.

View full text Add to dashboard Cite

Background: Lung adenocarcinoma (LUAD) is an aggressive disease of heterogeneous characteristics with poor prognosis and high mortality. Pyroptosis, a newly uncovered type of programmed cell death with an inflammatory nature, has been determined to hold substantial importance in the progression of tumors. Despite this, the knowledge about pyroptosis-related genes (PRGs) in LUAD is limited. This study aimed to develop and validate a prognostic signature for LUAD based on PRGs.Methods: In this research, gene expression information from The Cancer Genome Atlas (TCGA) served as the training cohort and data from Gene Expression Omnibus (GEO) was utilized as the validation cohort. PRGs list was taken from the Molecular Signatures Database (MSigDB) and previous studies. Univariate Cox regression and Lasso analysis were then conducted to identify prognostic PRGs and develop a LUAD prognostic signature. The Kaplan-Meier method, univariate and multivariate Cox regression models were employed to assess the independent prognostic value and forecasting accuracy of the pyroptosis-related prognostic signature. The correlation between prognostic signature and immune infiltrating was analyzed to examine the role in tumor diagnosis and immunotherapy. Further, RNA-seq as well as quantitative real-time polymerase chain reaction (qRT-PCR) analysis in separate data sets was applied in order to validate the potential biomarkers for LUAD.Results: A novel prognostic signature based on 8 PRGs (BAK1, CHMP2A, CYCS, IL1A, CASP9, NLRC4, NLRP1, and NOD1) was established to predict the survival of LUAD. The prognostic signature proved to be an independent prognostic factor of LUAD with satisfactory sensitivity and specificity in the training and validation sets. High-risk scores subgroups in the prognostic signature were significantly associated with advanced tumor stage, poor prognosis, less immune cell infiltration, and immune function deficiency. RNA sequencing and qRT-PCR analysis confirmed that the expression of CHMP2A and NLRC4 could be used as biomarkers for LUAD.Conclusion: We have successfully developed a prognostic signature consisting of eight PRGs that providing a novel perspective on predicting prognosis, assessing infiltration levels of tumor immune cells, and determining the outcomes of immunotherapy for LUAD.

show abstract

Section: Discussionmentioning

confidence: 99%

A novel pyroptosis-related prognostic signature for lung adenocarcinoma: Identification and multi-angle verification

Wang

Zhou

et al. 2023

Front. Genet.

View full text Add to dashboard Cite

show abstract

“…CHMP2A mediates tumor resistance to NK cells by the secretion of extracellular vesicles (EVs) expressing MHC class I chain‐related protein A and B as well as TRAIL. Loss of CHMP2A activates NF‐κB in tumor cells and increases chemokine secretion (CXCL10 and CXCL12), which promotes the recruitment of NK cells to tumors 123 (Figure 2A).…”

Section: Potential Targets Modulating Tumor Immune Responsementioning

confidence: 99%

Targets of tumor microenvironment for potential drug development

Zhang,

Wang,

Liu

et al. 2024

MedComm – Oncology

View full text Add to dashboard Cite

The tumor microenvironment (TME) is the ecosystem surrounding a tumor, which usually consists of nontumoral cells or components, and molecules they produce and release. The frequent and continuous interplay between tumor cells and the TME strongly affects tumor development, disease progression, metastasis, and responses to therapeutic interventions. As a hub of potential therapeutic targets, the TME has gained appreciable momentum in cancer research. Here we systematically review the progress in targeting the TME as a strategy to develop novel antitumor drugs from the immunological, stromal and extracellular matrix components of the TME, shedding light on its complex synergies with tumor cells. This exploration highlights the transformative potential these elements hold in refining cancer treatment approaches. This thorough examination not only accentuates the TME's multifaceted nature but also positions it as a formidable avenue for propelling forward the paradigms of cancer therapy. This review aims to foster a deeper understanding of the TME's role in oncogenesis and its potential exploitation in advancing targeted, efficacious cancer treatments, marking a significant stride in the realm of cancer research.

show abstract

“…One‐way tumor cells evade NK cell recognition through the loss of expression of various ligands activating NK cells including NK cell receptor DNAM‐1 ligand CD155 [54] and non‐MHC ligand CD48 [56]. Consistent with inhibitory effect of MHC‐I on NK cells, various in vitro CRISPR screens have confirmed the loss of antigen presentation (HLA‐A/B/C/E, TAP1, and TAP2) and interferon‐γ‐signaling pathways (IFNγR2, JAK2, and STAT1) enhance NK cells induced killing [57–59]. Although inhibiting IFNγ sounds like an attractive strategy [51,53], the application should proceed with caution as IFNγ loss can promote tumor immune evasion from CD8+ T cells [34].…”

Section: Application Of Crispr Screens For Immunotherapy Target Disco...mentioning

confidence: 99%

Tumor immune evasion: insights from CRISPR screens and future directions

Djajawi,

Wichmann,

Vervoort

et al. 2023

The FEBS Journal

View full text Add to dashboard Cite

Despite the clinical success of cancer immunotherapies including immune checkpoint blockade (ICB) and adoptive cellular therapies (ACTs) across a variety of cancer types, many patients do not respond or ultimately relapse, however, the molecular underpinnings of this are not fully understood. Thus, a systems level understating of the routes to tumor immune evasion is required to inform the design of the next generation of immunotherapy approaches. CRISPR screening approaches have proved extremely powerful in identifying genes that promote tumor immune evasion or sensitize tumor cells to destruction by the immune system. These large‐scale efforts have brought to light decades worth of fundamental immunology and have uncovered the key immune‐evasion pathways subverted in cancers in an acquired manner in patients receiving immune‐modulatory therapies. The comprehensive discovery of the main pathways involved in immune‐evasion has spurred the development and application of novel immune‐therapies to target this process. Although successful, conventional CRISPR‐screening approaches are hampered by a number of limitations which obfuscate a complete understanding of the precise molecular regulation of immune‐evasion in cancer. Here, we provide a perspective on screening approaches to interrogate tumor‐lymphocyte interactions and their limitations, and discuss further development of technologies to improve such approaches and discovery capability.

show abstract

CHMP2A regulates tumor sensitivity to natural killer cell-mediated cytotoxicity

Cited by 35 publications

References 78 publications

A novel pyroptosis-related prognostic signature for lung adenocarcinoma: Identification and multi-angle verification

A novel pyroptosis-related prognostic signature for lung adenocarcinoma: Identification and multi-angle verification

Targets of tumor microenvironment for potential drug development

Tumor immune evasion: insights from CRISPR screens and future directions

Contact Info

Product

Resources

About