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Plexin domain-containing 1 may be a biomarker of poor prognosis in hepatocellular carcinoma patients,may mediate immune evasion

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 2091-2112页

作者： Ming-Yue Tang Xue Shen Run-Sheng Yuan Hui-Yuan Li Xin-Wei Li Yi-Ming Jing Yue Zhang Hong-Hong Shen Zi-Shu Wang Lei Zhou Yun-Chuan Yang He-Xin Wen Fang Su Department of Medical Oncology The First Affiliated Hospital of Bengbu Medical CollegeBengbu 233000Anhui ProvinceChina Otolaryngology and Head and Neck Surgery The First Affiliated Hospital of Bengbu Medical CollegeBengbu 233000Anhui ProvinceChina Department of Neurology The First Affiliated Hospital of Bengbu Medical CollegeBengbu 233000Anhui ProvinceChina Department of Hepatobiliary Surgery The First Affiliated Hospital of Bengbu Medical CollegeBengbu 233000Anhui ProvinceChina Department of Gastrointestinal Surgery The First Affiliated Hospital of Bengbu Medical CollegeBengbu 233000Anhui ProvinceChina

BACKGROUND For the first time,we investigated the oncological role of plexin domain-containing 1(PLXDC1),also known as tumor endothelial marker 7(TEM7),in hepatocellular carcinoma(HCC).AIM To investigate the oncological profile of PLXDC1 in *** Based on The Cancer Genome Atlas database,we analyzed the expression of PLXDC1 in *** immunohistochemistry,quantitative real-time polymerase chain reaction(qRT-PCR),and Western blotting,we validated our *** prognostic value of PLXDC1 in HCC was analyzed by assessing its correlation with clinicopathological features,such as patient survival,methylation level,tumor immune microenvironment features,and immune cell surface checkpoint ***,to assess the immune evasion potential of PLXDC1 in HCC,we used the tumor immune dysfunction and exclusion(TIDE)website and immunohistochemical staining *** Based on immunohistochemistry,qRT-PCR,and Western blot assays,overexpression of PLXDC1 in HCC was associated with poor *** and multivariate Cox analyses indicated that PLXDC1 might be an independent prognostic *** HCC patients with high methylation levels,the prognosis was worse than in patients with low methylation *** enrichment analysis of HCC tissues indicated that genes upregulated in the high-PLXDC1 subgroup were enriched in mesenchymal and immune activation signaling,and TIDE assessment showed that the risk of immune evasion was significantly higher in the high-PLXDC1 subgroup compared to the low-PLXDC1 *** high-risk group had a significantly lower immune evasion rate as well as a poor prognosis,and PLXDC1-related risk scores were also associated with a poor *** As a result of this study analyzing PLXDC1 from multiple biological perspectives,it was revealed that it is a biomarker of poor prognosis for HCC patients,and that it plays a role in determining immune evasion status.

关键词： Plexin domain-containing 1 Biomarker immune evasion Prognosis Immunotherapy Hepatocellular carcinoma

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Protein tyrosine phosphatase non-receptor Ⅱ:A possible biomarker of poor prognosis and mediator of immune evasion in hepatocellular carcinoma

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World Journal of Gastrointestinal Oncology 2024年第9期16卷 3913-3931页

作者： Hui-Yuan Li Yi-Ming Jing Xue Shen Ming-Yue Tang Hong-Hong Shen Xin-Wei Li Zi-Shu Wang Fang Su Department of Medical Oncology The First Affiliated Hospital of Bengbu Medical UniversityBengbu 233000Anhui ProvinceChina Department of Neurology The First Affiliated Hospital of Bengbu Medical UniversityBengbu 233000Anhui ProvinceChina

BACKGROUND The incidence of primary liver cancer is increasing year by *** 2022 alone,more than 900000 people were diagnosed with liver cancer worldwide,with hepatocellular carcinoma(HCC)accounting for 75%-85%of *** is the most common primary liver *** has the highest incidence and mortality rate of HCC in the world,and it is one of the malignant tumors that seriously threaten the health of Chinese *** onset of liver cancer is occult,the early cases lack typical clinical symptoms,and most of the patients are already in the middle and late stage when ***,it is very important to find new markers for the early detection and diagnosis of liver cancer,improve the therapeutic effect,and improve the prognosis of *** tyrosine phosphatase non-receptor 2(PTPN2)has been shown to be associated with colorectal cancer,triple-negative breast cancer,non-small cell lung cancer,and prostate cancer,but its biological role and function in tumors remain to be further *** To combine the results of relevant data obtained from The Cancer Genome Atlas(TCGA)to provide the first in-depth analysis of the biological role of PTPN2 in *** The expression of PTPN2 in HCC was first analyzed based on the TCGA database,and the findings were then verified by immunohistochemical staining,quantitative real-time polymerase chain reaction(qRT-PCR),and *** value of PTPN2 in predicting the survival of patients with HCC was assessed by analyzing the relationship between PTPN2 expression in HCC tissues and clinicopathological ***,the potential of PTPN2 affecting immune escape of liver cancer was evaluated by tumor immune dysfunction and exclusion and immunohistochemical *** The results of immunohistochemical staining,qRT-PCR,and immunoblotting in combination with TCGA database analysis showed that PTPN2 was highly expressed and associated with a poor prognosis in HCC *** Encyclopedia of Ge

关键词： Protein tyrosine phosphatase non-receptor 2 Hepatocellular carcinoma immune evasion Biomarker Immunotherapy Prognosis

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Accurate Diagnosis of SARS-CoV-2 JN.1 by Sanger Sequencing of Receptor-Binding Domain Is Needed for Clinical Evaluation of Its immune evasion

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Journal of Biosciences and Medicines 2024年第4期12卷 69-78页

作者： Sin Hang Lee Milford Molecular Diagnostics Laboratory Milford CT USA

Background: Omicron JN.1 has become the dominant SARS-CoV-2 variant in recent months. JN.1 has the highest number of amino acid mutations in its receptor binding domain (RBD) and has acquired a hallmark L455S mutation. The immune evasion capability of JN.1 is a subject of scientific investigation. The US CDC used SGTF of TaqPath COVID-19 Combo Kit RT-qPCR as proxy indicator of JN.1 infections for evaluation of the effectiveness of updated monovalent XBB.1.5 COVID-19 vaccines against JN.1 and recommended that all persons aged ≥ 6 months should receive an updated COVID-19 vaccine dose. Objective: Recommend Sanger sequencing instead of proxy indicator to diagnose JN.1 infections to generate the data based on which guidelines are made to direct vaccination policies. Methods: The RNA in nasopharyngeal swab specimens from patients with clinical respiratory infection was subjected to nested RT-PCR, targeting a 398-base segment of the N-gene and a 445-base segment of the RBD of SARS-CoV-2 for amplification. The nested PCR amplicons were sequenced. The DNA sequences were analyzed for amino acid mutations. Results: The N-gene sequence showed R203K, G204R and Q229K, the 3 mutations associated with Omicron BA.2.86 (+JN.1). The RBD sequence showed 24 of the 26 known amino acid mutations, including the hallmark L455S mutation for JN.1 and the V483del for BA.2.86 lineage. Conclusions: Sanger sequencing of a 445-base segment of the SARS-CoV-2 RBD is useful for accurate determination of emerging variants. The CDC may consider using Sanger sequencing of the RBD to diagnose JN.1 infections for statistical analysis in making vaccination policies.

关键词： Omicron JN.1 SARS-CoV-2 Sanger Sequencing RBD L455S Mutation immune evasion Vaccination Policies CDC

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immune evasion mechanisms and therapeutic strategies in gastric cancer

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World Journal of Gastrointestinal Oncology 2022年第1期14卷 216-229页

作者： En-Si Ma Zheng-Xin Wang Meng-Qi Zhu Jing Zhao Department of General Surgery Huashan HospitalFudan UniversityShanghai 200040China Institute of Organ Transplantation Fudan UniversityShanghai 200040China Department of Infectious Diseases Huashan HospitalFudan UniversityShanghai 200040China Cancer Metastasis Institute Fudan UniversityShanghai 200040China

Gastric cancer(GC)is a malignancy with a high incidence and *** tumor immune microenvironment plays an important role in promoting cancer development and supports GC *** evidence shows that GC cells can exert versatile mechanisms to remodel the tumor immune microenvironment and induce immune *** this review,we systematically summarize the intricate crosstalk between GC cells and immune cells,including tumor-associated macrophages,neutrophils,myeloid-derived suppressor cells,natural killer cells,effector T cells,regulatory T cells,and B *** focus on how GC cells alter these immune cells to create an immunosuppressive microenvironment that protects GC cells from immune *** conclude by compiling the latest progression of immune checkpoint inhibitor-based immunotherapies,both alone and in combination with conventional ***-cytotoxic Tlymphocyte-associated protein 4 and anti-programmed cell death protein 1/programmed death-ligand 1 therapy alone does not provide substantial clinical benefit for GC ***,the combination of immune checkpoint inhibitors with chemotherapy or targeted therapy has promising survival advantages in refractory and advanced GC *** review provides a comprehensive understanding of the immune evasion mechanisms of GC,and highlights promising immunotherapeutic strategies.

关键词： Gastric cancer immune evasion immune checkpoint Immunotherapy Microenvironment

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Targeting pancreatic cancer immune evasion by inhibiting histone deacetylases

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World Journal of Gastroenterology 2022年第18期28卷 1934-1945页

作者： Wynne Sim Wei-Meng Lim Ling-Wei Hii Chee-Onn Leong Chun-Wai Mai School of Medicine International Medical UniversityKuala Lumpur 57000Malaysia School of Pharmacy International Medical UniversityKuala Lumpur 57000Malaysia Center for Cancer and Stem Cell Research Institute for ResearchDevelopmentand InnovationInternational Medical UniversityKuala Lumpur 57000Malaysia AGTC Genomics Kuala Lumpur 57000Malaysia State Key Laboratory of Oncogenes and Related Genes Renji-Med X Clinical Stem Cell Research CenterRen Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200127China Department of Pharmaceutical Chemistry Faculty of Pharmaceutical SciencesUCSI UniversityKuala Lumpur 56000Malaysia

The immune system plays a vital role in maintaining the delicate balance between immune recognition and tumor ***,it is not uncommon that cancerous cells can intelligently acquire abilities to bypass the antitumor immune responses,thus allowing continuous tumor growth and *** evasion has emerged as a significant factor contributing to the progression and immune resistance of pancreatic *** with other cancers,pancreatic cancer has a tumor microenvironment that can resist most treatment modalities,including emerging ***,the use of immunotherapy has yet to bring significant clinical breakthrough among pancreatic cancer patients,suggesting that pancreatic cancer has successfully evaded *** this review,we summarize the impact of genetic alteration and epigenetic modification(especially histone deacetylases,HDAC)on immune evasion in pancreatic *** overexpression significantly suppresses tumor suppressor genes,contributing to tumor growth and *** review the evidence on HDAC inhibitors in tumor eradication,improving T cells activation,restoring tumor immunogenicity,and modulating programmed death 1 *** provide our perspective in targeting HDAC as a strategy to reverse immune evasion in pancreatic cancer.

关键词： Histone acetylation Histone deacetylases inhibitors immune evasion Pancreatic cancers Pancreatic ductal adenocarcinoma

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immune evasion and therapeutic opportunities based on natural killer cells

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Chinese Journal of Cancer Research 2023年第3期35卷 283-298页

作者： Jinjin Zhang Feifei Guo Lingyu Li Songling Zhang Yufeng Wang Cancer Center The First Hospital of Jilin UniversityChangchun 130021China Department of Gynecology Obstetrics and Gynecology CenterThe First Hospital of Jilin UniversityChangchun 130021China Department of Gynecological Oncology Obstetrics and Gynecology CenterThe First Hospital of Jilin UniversityChangchun 130021China

Natural killer(NK)cells can elicit an immune response against malignantly transformed cells without recognizing antigens,and they also exhibit cytotoxic effects and immune surveillance functions in tumor *** several studies have shown the promising antitumor effects of NK cells in immunotherapy,their function is often limited in the tumor microenvironment because tumor cells can easily escape NK cell-induced ***,for efficient tumor immunotherapy,the mechanism by which tumor cells escape NK cell-induced cytotoxicity must be fully *** novel molecules and checkpoint receptors that mediate the disruption of NK cells in the tumor microenvironment have been *** this review,we analyze and detail the major activating and inhibitory receptors on the surface of NK cells to delineate the mechanism by which tumor cells suppress NKG2D ligand expression and increase tumor receptor and inhibitory receptor expression[NKG2A,programmed cell death1(PD-1),and T-cell immunoglobulin and immunoreceptor tyrosine inhibitory motif(TIGIT)]on the NK cell surface,and thus inhibit NK cell *** also reviewed the current status of treatments based on these surface *** comparing the therapeutic effects related to the treatment status and bypass mechanisms,we attempt to identify optimal single or combined treatments to suggest new treatment strategies for tumor immunotherapy.

关键词： immune evasion natural killer cell NKG2D PD-1 combination therapy

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EXPRESSION OF FLIP IN HUMAN COLON CARCINOMAS: A NEW MECHANISM OF immune evasion

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Chinese Journal of Cancer Research 2005年第3期17卷 193-198页

作者：邢宝才 S. Wimmenauer EH. Farthmann Department of Surgery Peking University School of Oncology Beijing Cancer Hospital Beijing Institute for Cancer Research Department of Surgery University Hospital of Freiburg

Objective： It has been proposed that Fas ligand （FasL） may play an important role in immune escape of tumors and FLIP is an important mediator of Fas/FasL pathway. In this study, the expression of FLIP was determined in human colon carcinoma cell lines and tissue to investigate the new mechanism of immune evasion of human colon carcinomas. Methods： RT-PCR and immunohistochemistry （IHC） were performed to investigate the expression of FLIP in human colon carcinoma cell lines SW480, LS174 and twenty human primary colon carcinoma specimens. Results： It was shown that SW480 cells, LS174 cells and primary colon carcinoma specimen constitutively expressed FLIP at the mRNA and protein level. The expression of FLIP was not found in the epithelial cells of normal colon mucosa. Conclusion： FLIP was expressed in human primary colon carcinoma specimens but not in the normal counterpart. It suggested that the expression of FLIP may occur during the malignant transformation from normal colon epithelial cells to colon carcinoma cells. Tumor cells might obtain the ability to resist the Fas-mediated apoptosis by expressing FLIP. The expression of FLIP might contribute to the formation of colon carcinomas.

关键词： Colon carcinoma Fas/FasL FLIP immune evasion

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Germline genomes have a dominant-heritable contribution to cancer immune evasion and immunotherapy response

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Quantitative Biology 2020年第3期8卷 216-227页

作者： Xue Jiang Mohammad Asad Lin Li Zhanpeng Sun Jean-Sebastien Milanese Bo Liao Edwin Wang Shanghai Mental Health Center School of Biomedical EngineeringShanghai Jiao Tong UniversityShanghai 200030China Department of Biochemistry and Molecular Biology Cumming School of MedicineUniversity of CalgaryCalgaryT2N 4N1Canada Tianjin Normal University Tianjin 300074China Human Health Therapeutics Research Centre National Research Council CanadaMontrealH4P 2R2Canada School of Mathematics and Statistics Hainan Normal UniversityHaikou 570206China

Background:immune evasion is a fundamental hallmark for *** the early stages of tumor development,immune evasion strategies must be implemented by tumors to prevent attacks from the host immune *** tumors5 immune evasion will re-activate the host immune systems to eliminate ***-checkpoint therapy(ICT)which applies anti-PD-l/PD-Ll or anti-CTLA4 treatment has been a remarkable success in the past few ***,〜70%of patients cannot gain any clinical benefits from ICT treatment due to the tumorimmunity system's complexity・In the past,germline pathogenic variants have been thought to have only minorheritable contributions to ***:Emerging evidence has shown that germline genomes play a dominant-heritable contribution to cancer via encoding the host immune *** functional components of the immune system are encoded by the host genome,thus the germline genome might have a profound impact on cancer immune evasion and immunotherapy ***,recent studies showed that germline pathogenic variants can influence immune capacity in cancer patients at a population level by(i)shaping tumor somatic mutations,altering methylation patterns and antigen-presentation capacity or(ii)influencing NK cell's function to modulate lymphocyte infiltration in the tumor *** addition,the HLA(types A,B or C)genotypes also shape the landscape of tumor somatic ***:These results highlight the indispensable roles of germline genome in immunity and cancer development and suggest that germline genomics should be integrated into the research field of cancer biology and cancer immunotherapy.

关键词： germline genomics cancer immune evasion immunotherapy response

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Prognostic value of lactate transporter SLC16A1 and SLC16A3 as oncoimmunological biomarkers associating tumor metabolism and immune evasion in glioma

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Cancer Innovation 2022年第3期1卷 229-239页

作者： Ting Zhu Xiaoqin Ge Shengping Gong Shenchao Guo Qingsong Tao Jianxin Guo Ruishuang Ma Department of Radiotherapy and Chemotherapy Ningbo First HospitalNingboChina Central Laboratory of the Medical Research Center Ningbo First HospitalNingboChina

Background:Hypoxic microenvironment is immunosuppressive and protu-morigenic,and elevated lactate is an intermediary in the modulation of immune ***,as critical lactate transporters,the role of SLC16A1 and SLC16A3 in immune infiltration and evasion of glioma is not fully ***:Gene expression in low‐and high‐grade glioma(LGG and GBM)was evaluated with TCGA *** TISIDB,TIMER and CIBERSORT databases were utilized for the analysis of the correlation between SLC16A1 or SLC16A3 and immunocyte infiltration as well as immune ***:Compared with normal tissues,a significant increase of both SLC16A1 and SLC16A3 was found in LGG and GBM,and closely related to the poor prognosis only in *** SEA indicated that SLC16A1 was involved in hypoxia while SLC16A3 contributed to metastasis and inflamma-tion in *** SLC16A3 expression was significantly correlated with neutrophil activation by GO *** showed the distribution of SLC16A1 on glioma cells and SLC16A3 on immune cells,which was correlated to tumor‐associated macrophages and neutrophils that are ***16A1 and SLC16A3 were identified to tightly interacted with diverse immune checkpoints(especially PD1,PD‐L1,PD‐L2,Tim‐3)and immunosuppressive factors(TGF‐βand IL‐10)in ***,SLC16A3 had a positive correlation to activation markers of tumor‐associated neutrophils and chemokines such as CCL2,CCL22,CXCR2,CXCR4 in LGG and CCL7,CCL20 CXCL8 in GBM,which could enhance infiltration of immunosuppressive cells to the tumor ***:In general,our results suggest that SLC16A1 and SLC16A3 act as a bridge between tumor metabolism and immunity by promoting immuno-suppressive cell infiltration,which contributes to immune evasion and a worse prognosis in *** SLC16A1 and SLC16A3 may provide novel therapeutic strategy for immunotherapy in glioma.

关键词： glioma SLC16A1(MCT1) SLC16A3(MCT4) immune checkpoints immune evasion

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Cytomegalovirus immune evasion by perturbation ot endosomal trafficking

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Cellular & Molecular Immunology 2015年第2期12卷 154-169页

作者： Pero Lucin Hana Mahmutefendic Gordana Blagojevic Zagorac Maja Ilic Tomas Department of Physiology and Immunology University of Rijeka Faculty of Medicine Rijeka Croatia

Cytomegaloviruses （CMVs）, members of the herpesvirus family, have evolved a variety of mechanisms to evade the immune response to survive in infected hosts and to establish latent infection, They effectively hide infected cells from the effector mechanisms of adaptive immunity by eliminating cellular proteins （major histocompatibility Class I and Class II molecules） from the cell surface that display viral antigens to CD8 and CD4 T lymphocytes, CMVs also successfully escape recognition and elimination of infected cells by natural killer （NK） cells, effector cells of innate immunity, either by mimicking NK cell inhibitory ligands or by downregulating NK cell-activating ligands, To accomplish these immunoevasion functions, CMVs encode several proteins that function in the biosynthetic pathway by inhibiting the assembly and trafficking of cellular proteins that participate in immune recognition and thereby, block their appearance at the cell surface, However, elimination of these proteins from the cell surface can also be achieved by perturbation of their endosomal route and subsequent relocation from the cell surface into intracellular compartments, Namely, the physiological route of every cellular protein, including immune recognition molecules, is characterized by specific features that determine its residence time at the cell surface, In this review, we summarize the current understanding of endocytic trafficking of immune recognition molecules and perturbations of the endosomal system during infection with CMVs and other members of the herpesvirus family that contribute to their immune evasion mechanisms,

关键词： cytomegaloviruses endocytic trafficking herpesviruses immune evasion

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