We are analyzing https://link.springer.com/article/10.1007/s00432-023-05268-y.

Title:
Integrated single-cell and bulk sequencing analyses with experimental validation identify the prognostic and immunological implications of CD226 in pan-cancer | Journal of Cancer Research and Clinical Oncology
Description:
Purpose CD226 (DNAM-1) is an activating receptor mainly expressed in CD8 + and NK cells. CD226 deficiency and blockade have been shown to impair tumor suppression, while enhanced CD226 expression positively correlated with the increased efficacy of immune checkpoint blockade (ICB) therapies. However, the detailed function and role of CD226 in pan-cancer are largely unknown and require further in-depth investigation. Therefore, this study aims to investigate the biological functions of CD226, its role in tumor immunity, and its potential to predict prognosis and immunotherapy response in pan-cancer. Methods By taking advantage of single-cell and bulk sequencing analyses, we analyzed the expression profile of CD226, its correlation with patient prognosis, immune infiltration level, immune-related genes, tumor heterogeneity, and stemness in pan-cancer. We also investigated the biological functions of CD226 using gene set enrichment analysis (GSEA) and evaluated its predictive value in response to immunotherapy and small-molecule targeted drugs. In addition, we validated the expression of CD226 in tumor-infiltrating CD8 + and NK cells and studied its association with their functions using a murine B16F10 melanoma model. Results CD226 exhibited differential expression across most tumor types, and its elevated expression was associated with improved clinical outcomes in multiple cancer types. CD226 is closely correlated with numerous tumor-infiltrating immune cells, tumor stemness, and heterogeneity in most cancers. Furthermore, based on single-cell sequencing analysis, CD226 expression was found to be higher on effector CD4 + T cells than naïve CD4 + T cells, and its expression level was decreased in exhausted CD8 + T cells relative to effector CD8 + T cells in multiple cancer types. Additionally, flow cytometric analysis demonstrated that CD226 was highly correlated with the function of tumor-infiltrating NK and CD8 + T cells in murine B16F10 melanoma. Moreover, GSEA analysis revealed that CD226 was closely associated with T cell activation, natural killer cell mediated immunity, natural killer cell-mediated cytotoxicity, and T cell receptor signaling pathway. Finally, CD226 showed promising predictive potential for responsiveness to both ICB therapies and various small-molecule targeted drugs. Conclusion CD226 has shown great potential as an innovative biomarker for predicting patient prognosis, immune infiltration levels, and the function of tumor-infiltrating CD8 + T cells, as well as immunotherapy response. Additionally, our findings suggest that the optimal modification of CD226 expression and function, combined with current ICBs, could be a promising strategy for tumor immunotherapy.
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pubmed, article, google, scholar, cancer, cas, central, cells, immunotherapy, cell, tumor, analysis, immune, immunity, pancancer, expression, tumorinfiltrating, res, data, potential, prognosis, function, research, sun, response, immunol, analyses, receptor, cancers, access, antitumor, oncol, sci, privacy, cookies, content, information, journal, publish, clinical, singlecell, prognostic, blockade, study, types, natural, killer, human, author, med,

Topics {✒️}

user-uploaded gene/measurement sets tigit/pvrig/tactile axis month download article/chapter tumor-immune system interactions single-cell transcriptome analyses small-molecule targeted drugs customizable protein-protein networks cell anti-tumor functions tissue-dependent tumor microenvironments optimize anti-tumor cd8 single-cell sequencing analysis tumor-infiltrating immune cells tigit-cd226-pvr axis mapk/erk pathways involved pan-cancer analysis shows pan-cancer research published full article pdf accepted manuscript version 2024 tumor-infiltrating cd226+cd8+ tumor-infiltrating nk activating receptor cd226 integrated single-cell immune-related genes clinical oncology aims article ma anti-tigit immunotherapy privacy choices/manage cookies improved clinical outcomes integrated repository portal mapk signaling pathways immune checkpoint blockade immune infiltration levels pd-1/pd-l1 tumor microenvironment megakaryocytic cell adhesion phosphorylation-mediated inactivation model tumor immunity related subjects immune infiltration level bulk sequencing analyses tumor-infiltrating cd8 + lung cancer stem weili sun impair tumor suppression multiple cancer types cd226 opposes tigit distinct gene module activating receptor amplify tcr signals lymphocyte receptors involved

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Farkona S, Diamandis EP, Blasutig IM (2016) Cancer immunotherapy: the beginning of the end of cancer?

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