COPS6 promotes tumor progression and reduces CD8+ T cell infiltration by repressing IL-6 production to facilitate tumor immune evasion in breast cancer

Du, Wen‐Qi; Zhu, Zhansheng; Jiang, Xin; Kang, Meng-jie; Pei, Dong‐Sheng

doi:10.1038/s41401-023-01085-8

Cited by 5 publications

(4 citation statements)

References 46 publications

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“…The findings of the present study demonstrated a negative correlation between COPS6 expression level and CD8+ T cell infiltration in several tumors, such as BRCA, HNSC, and TGCT. This aligns with Du et al [ 28 ]’s results, demonstrating that COPS6 could inhibit CD8+ T cell infiltration within the tumor microenvironment (TME), thereby facilitating tumor immune evasion. Furthermore, a negative correlation was identified between COPS6 expression level and the M1 phenotype of tumor-associated macrophages (TAMs), while a positive correlation was found with the M2 phenotype.…”

Section: Discussionsupporting

confidence: 91%

Computational exploration of the significance of COPS6 in cancer: Functional and clinical relevance across tumor types

Wang,

Zhuo,

Wang

et al. 2023

World J Clin Oncol

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BACKGROUND The COP9 signalosome subunit 6 (COPS6 ) has been implicated in cancer progression, while its precise role in most types of cancer remains elusive. AIM To investigate the functional and clinical relevance of COPS6 across various tumor types using publicly available databases. METHODS We used R software and online analysis databases to analyze the differential expression, prognosis, mutation and related functions of COPS6 in pan-cancer. RESULTS Differential expression analysis and survival analysis demonstrated that COPS6 was highly expressed and associated with high-risk profiles in the majority of cancer types. Possible associations between COPS6 expression level and prognostic outcomes were found using data from public databases. Mutational analysis revealed that missense mutations were the predominant type of COPS6 mutation. Additionally, positive correlations were identified between COPS6 expression level and tumor mutational burden and microsatellite instability in most types of cancer. Immune infiltration analysis demonstrated a negative correlation between COPS6 expression level and CD8+ T cell infiltration in certain types of cancer. The correlation between COPS6 expression level and cancer-associated fibroblast infiltration exhibited heterogeneity, in which a positive correlation was found in head and neck squamous cell carcinoma and tenosynovial giant cell tumor, and a negative correlation was identified in diffuse large B-cell lymphoma and thymoma. The correlation between COPS6 expression level and macrophage infiltration was closely related to macrophage type. Gene co-expression and enrichment analysis highlighted transcription elongation factor B polypeptide 2 and G protein pathway suppressor 1 were significantly and positively associated with COPS6 expression level. These genes were predominantly involved in processes, such as ubiquitin-mediated proteolysis and human immunodeficiency virus 1 infection. CONCLUSION In conclusion, this study systematically explored the significance of COPS6 across different tumor types, providing a solid foundation for considering COPS6 as a novel biomarker in cancer research.

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Section: Discussionsupporting

confidence: 91%

Computational exploration of the significance of COPS6 in cancer: Functional and clinical relevance across tumor types

Wang,

Zhuo,

Wang

et al. 2023

World J Clin Oncol

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“…PSMD4, functioning as a ubiquitin-degrading enzyme within the proteasome’s 19S regulatory granules, can control numerous biological processes, such as the stability of proteins, the advancement of cancer, and resistance to drugs [ 43 ]. COPS6, a member of the JAMM family, has recently been verified to facilitate tumor advancement and decrease the infiltration of CD8 + T-cells by suppressing the synthesis of IL-6, thus promoting tumor immune escape from cancer [ 44 , 45 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of a novel matrix metalloproteinases-related prognostic signature in hepatocellular carcinoma

Yuan,

Yang,

Gao

et al. 2024

Aging

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Background: Hepatocellular carcinoma (HCC) is the most common primary liver cancer worldwide. Cancer cells’ local infiltration, proliferation, and spread are mainly influenced by the protein hydrolyzing function of different matrix metalloproteinases (MMPs). However, no study has determined the relationship between MMPs and prognostic prediction in HCC. Methods: Expression profiles of mRNA and MMPs-related genes were obtained from publicly available databases. Cox regression and LASSO Cox regression analysis were used to identify and predict MMPs-related prognostic signature and construct predictive models for overall survival (OS). A nomogram was used to validate the accuracy of the prediction model. Drug prediction was performed using the Genomics of Drug Sensitivity in Cancer (GDSC) dataset, and single-cell clustering analysis was performed to further understand the significance of the MMPs-related signature. Results: A MMPs-related prognostic signature (including RNPEPL1, ADAM15, ADAM18, ADAMTS5, CAD, YME1L1, AMZ2, PSMD14, and COPS6) was identified. Using the median value, HCC patients in the high-risk group showed worse OS than those in the low-risk group. Immune microenvironment analysis showed that patients in the high-risk group had higher levels of M0 and M2 macrophages. Drug sensitivity analysis revealed that the IC 50 values of sorafenib, cisplatin, and cytarabine were higher in the high-risk group. Finally, the single-cell cluster analysis results showed that YME1L1 and COPS6 were the major genes expressed in the monocyte cluster. Conclusions: A novel MMPs-related signature can be used to predict the prognosis of HCC. The findings of this research could potentially impact the predictability of the prognosis and treatment of HCC.

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“…Cancer cells can evade immune surveillance while preserving immunogenicity and continue to stimulate the immune system, initiating a series of aberrant immune behaviors that further assist in tumor immune escape [ 81 ]. For instance, the constant stimulation of tumor antigens motivates T cells to work persistently, eventually reaching a state of exhaustion [ 64 ].…”

Section: Cancer Immune Escape: In a Close Relation To Cd8 +...mentioning

confidence: 99%

CD8+ T cell-based cancer immunotherapy

Chen,

Yu,

Qian

et al. 2024

J Transl Med

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The immune system in humans is a defense department against both exogenous and endogenous hazards, where CD8+ T cells play a crucial role in opposing pathological threats. Various immunotherapies based on CD8+ T cells have emerged in recent decades, showing their promising results in treating intractable diseases. However, in the fight against the constantly changing and evolving cancers, the formation and function of CD8+ T cells can be challenged by tumors that might train a group of accomplices to resist the T cell killing. As cancer therapy stepped into the era of immunotherapy, understanding the physiological role of CD8+ T cells, studying the machinery of tumor immune escape, and thereby formulating different therapeutic strategies become the imperative missions for clinical and translational researchers to fulfill. After brief basics of CD8+ T cell-based biology is covered, this review delineates the mechanisms of tumor immune escape and discusses different cancer immunotherapy regimens with their own advantages and setbacks, embracing challenges and perspectives in near future.

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COPS6 promotes tumor progression and reduces CD8+ T cell infiltration by repressing IL-6 production to facilitate tumor immune evasion in breast cancer

Cited by 5 publications

References 46 publications

Computational exploration of the significance of COPS6 in cancer: Functional and clinical relevance across tumor types

Computational exploration of the significance of COPS6 in cancer: Functional and clinical relevance across tumor types

Identification of a novel matrix metalloproteinases-related prognostic signature in hepatocellular carcinoma

CD8+ T cell-based cancer immunotherapy

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