ArticleCancers2022
ACAP1 Deficiency Predicts Inferior Immunotherapy Response in Solid Tumors.
Article in Cancers, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
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- Targeting epigenetic regulators as a promising avenue to overcome cancer therapy resistance.Signal transduction and targeted therapy · 2025Review
- Potential common mechanisms between primary Sjögren's syndrome and Hashimoto's thyroiditis: a public databases-based study.Frontiers in genetics · 2025Article
- Decoding the Tumor Microenvironment of Myoepithelial Cells in Triple-Negative Breast Cancer Through Single-Cell and Transcriptomic Sequencing and Establishing a Prognostic Model Based on Key Myoepithelial Cell Genes.International journal of genomics · 2025Article
- Clinical Proteomics Reveals Vulnerabilities in Noninvasive Breast Ductal Carcinoma and Drives Personalized Treatment Strategies.Cancer research communications · 2025Article
- The T cell-mediated tumor killing patterns revealed tumor heterogeneous and proposed treatment recommendation in ovary cancer.Discover oncology · 2024Article
- GLN2 as a key biomarker and therapeutic target: evidence from a comprehensive pan-cancer study using molecular, functional, and bioinformatic analyses.Discover oncology · 2024Article
- Recent Advancements in Research on DNA Methylation and Testicular Germ Cell Tumors: Unveiling the Intricate Relationship.Biomedicines · 2024Review
- IGF2BP3 prevent HMGB1 mRNA decay in bladder cancer and development.Cellular & molecular biology letters · 2024Article
- Construction of an anoikis-associated lncRNA-miRNA-mRNA network reveals the prognostic role of β-elemene in non-small cell lung cancer.Scientific reports · 2023Article
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Authors and funding
5 authors.
Funding
Abstract
backgroundACAP1 plays a key role in endocytic recycling, which is essential for the normal function of lymphocytes. However, the expression and function of ACAP1 in lymphocytes have rarely been studied.
methodsLarge-scale genomic data, including multiple bulk RNA-sequencing datasets, single-cell sequencing datasets, and immunotherapy cohorts, were exploited to comprehensively characterize ACAP1 expression, regulation, and function. Gene set enrichment analysis (GSEA) was used to uncover the pathways associated with ACAP1 expression. Eight algorithms, including TIMER, CIBERSORT, CIBERSORT-ABS, QUANTISEQ, xCELL, MCPCOUNTER, EPIC, and TIDE, were applied to estimate the infiltrating level of immune cells. Western blotting, qPCR, and ChIP-PCR were used to validate the findings from bioinformatic analyses. A T-cell co-culture killing assay was used to investigate the function of ACAP1 in lymphocytes.
resultsACAP1 was highly expressed in immune-related tissues and cells and minimally in other tissues. Moreover, single-cell sequencing analysis in tumor samples revealed that ACAP1 is expressed primarily in tumor-infiltrating lymphocytes (TILs), including T, B, and NK cells. ACAP1 expression is negatively regulated by promoter DNA methylation, with its promoter hypo-methylated in immune cells but hyper-methylated in other cells. Furthermore, SPI1 binds to the ACAP1 promoter and positively regulates its expression in immune cells. ACAP1 levels positively correlate with the infiltrating levels of TILs, especially CD8+ T cells, across a broad range of solid cancer types. ACAP1 deficiency is associated with poor prognosis and immunotherapeutic response in multiple cancer types treated with checkpoint blockade therapy (ICT). Functionally, the depletion of ACAP1 by RNA interference significantly impairs the T cell-mediated killing of tumor cells.
conclusionsOur study demonstrates that ACAP1 is essential for the normal function of TILs, and its deficiency indicates an immunologically "cold" status of tumors that are resistant to ICT.
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