Effect of CCND1 amplification on immunosuppression and the association with a poor prognosis to immune checkpoint inhibitors in solid tumors
Abstract only e15249 Background: CCND1 amplification relevant to malignant biological behavior exist in solid tumors. The prevalence and utility of CCND1 amplification as a biomarker for the clinical response to immune checkpoint inhibitors (ICIs) therapy is unknown. Methods: This study included thr...
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Published in | Journal of clinical oncology Vol. 38; no. 15_suppl; p. e15249 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
20.05.2020
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Online Access | Get full text |
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Summary: | Abstract only
e15249
Background: CCND1 amplification relevant to malignant biological behavior exist in solid tumors. The prevalence and utility of CCND1 amplification as a biomarker for the clinical response to immune checkpoint inhibitors (ICIs) therapy is unknown. Methods: This study included three cohorts: Geneplus Institute ( n= 6536), The Cancer Genome Atlas ( n= 10562) and Memorial Sloan Kettering Cancer Center ( n= 106109). Comprehensive profiling was performed to determine the prevalence of CCND1 amplification and their correlation with the prognosis and the response to ICIs. Results: CCND1 amplification occurs in many cancer types, correlates with shorter overall survival and inferior outcomes with ICIs therapy. Transcriptomic analysis showed various degrees of immune cells exclusion, including cytotoxic cells, T cells, CD8
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T cells, DC cells, B cells in the tumor microenvironment (TME) in a CCND1 amplification population. The gene set enrichment analysis suggested that CCND1 amplification correlates with multiple aggressive, immunosuppressive hallmarks including epithelial mesenchymal transition, TGF-β signaling, KRAS signaling, PI3K/AKT/mTOR signaling, p53 pathway and hypoxia signaling in solid tumors. Conclusions: Our study indicated that CCND1 amplification may be a key point related to immunosuppression in TME and multiple malignancy hallmarks, and it hinders not only the natural host immune responses but also the efficacy of ICIs in solid tumors. |
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ISSN: | 0732-183X 1527-7755 |
DOI: | 10.1200/JCO.2020.38.15_suppl.e15249 |