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Regulation of CD137 expression through K-Ras signaling in pancreatic cancer cells

Cancer Communications 2019年第1期39卷 379-389页

作者： christophe glorieux Peng Huang Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhou 510060GuangdongP.R.China

Background:The interaction between CD137 and its ligand(CD137L)plays a major role in the regulation of immune functions and affects cancer ***137 is a cell surface protein mainly located on activated T cells,and its regulation and functions in immune cells are well ***,the expression of CD137 and its regulation in cancer cells remain poorly *** main purposes of this study were to examine the expression of CD137 in pancreatic cancer cells and to investigate its underlying ***:Cells containing inducible K-RasG12V expression vector or with different K-Ras mutational statuses were used as in vitro models to examine the regulation of CD137 expression by *** molecular assays were employed to explore the regulatory *** specimens from 15 pancreatic cancer patients and serum samples from 10 patients and 10 healthy donors were used to test if the expression of CD137 could be validated in clinical ***:We found that the CD137 protein was expressed on the cell surface in pancreatic cancer tissues and cancer cell ***-linked immunosorbent assay revealed no difference in the levels of secreted CD137 in the sera of patients and healthy *** using the K-Ras inducible cell system,we further showed that oncogenic K-Ras up-regulated CD137 through the activation of MAPK(mitogen-activated protein kinases)and NF-κB(nuclear factor kappa-light-chain-enhancer of activated B cells)pathways,as evidenced by significantly reduced CD137 mRNA expression led by genetic silencing of MAPK1 and p65,the key proteins involved in the respective ***-more,we also found that the NF-κB pathway was mainly stimulated by the K-Ras-induced secretion of interleukin-1α(IL-1α)which promoted the transcription of the CD137 gene in pancreatic cancer cell *** of the TCGA(the cancer genome atlas)database also revealed a significant correlation between IL-1αand CD137 expression(r=0.274)in tumor s

关键词： CD137 K-Ras IL-1α(interleukin-1 alpha) MAPK(mitogen-activated protein kinases) NF-κB(nuclear factor kappa-light-chain-enhancer of activated B cells) Pancreatic cancer Oxidative stress Soluble CD137

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CD137 expression in cancer cells:regulation and significance

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Cancer Communications 2019年第1期39卷 615-617页

作者： christophe glorieux Peng Huang State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineSun Yat-sen University Cancer CenterGuangzhou 510060GuangdongP.R.China

Evasion of immune surveillance is an important fea-ture of cancer,which expresses certain molecules that affect immune functions such as immune checkpoints[1].Among the molecules that impact the interactions between cancer and immune cells,PD-L1(programmed death-ligand 1)and CTLA-4(cytotoxic T-lymphocyte-associated protein 4)are well-known to modulate the immune system and play important roles in cancer *** tumor necrosis factor receptor superfamily member 9(TNFRSF9),also known as CD137 or 4-1BB,is another important immune-modulating molecule known to be expressed on the surface of certain immune ***137 was originally discovered in 1989 and reported as a cell surface protein mainly located on activated T cells[2].Interaction of CD137 with its ligand(CD137L,also known as TNFSF9 or 4-1BBL)on activated anti-gen-presenting cells(APCs)could lead to bidirectional activation that promotes immunity against cancer[3].For instance,it has been shown that signals through the CD137 receptor could lead to T cell activation and sur-vival[3].Reversely,engaged CD137L could impact its expressing cells,such as dendritic cells,leading to their activation and maturation[4].Hence,the use of agonistic CD137 antibodies such as urelumab and utomilumab is considered as a promising immunotherapeutic approach to treat various types of tumors[5].

关键词： CD137 cancer immunity

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Diverse effects of chemotherapeutic agents on immune cell function and implications in immunochemotherapy

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Cancer Communications 2021年第5期41卷 432-435页

作者： christophe glorieux Lei Cui Peiting Zeng Xiaojun Xia Peng Huang State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineSun Yat-sen University Cancer CenterGuangzhouGuangdong 510060P.R.China Metabolic Innovation Center Sun Yat-sen UniversityGuangzhouGuangdong 510080P.R.China

Dear Editor,Immunotherapy,such as the use of immune checkpoint blockade antibodies,has revolutionized cancer treatment resulting in a significant improvement of clinical outcome[1,2].As chemotherapeutic agents are still the major therapeutic modalities,their combination with immunotherapy is emerging as a newmulti-target strategy to eliminate cancer[3].However,it is still unclear which chemotherapeutic agents are most suitable for combination with immunotherapy.

关键词： therapeutic cancer immune

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