Cancer Microenvironment最新文献

Pyruvate Kinase M2: a Metabolic Bug in Re-Wiring the Tumor Microenvironment. 丙酮酸激酶M2：重新连接肿瘤微环境的代谢缺陷。

Cancer Microenvironment Pub Date : 2019-12-01 Epub Date: 2019-06-10 DOI: 10.1007/s12307-019-00226-0

Mohd Rihan, Lakshmi Vineela Nalla, Anil Dharavath, Amit Shard, Kiran Kalia, Amit Khairnar

{"title":"Pyruvate Kinase M2: a Metabolic Bug in Re-Wiring the Tumor Microenvironment.","authors":"Mohd Rihan, Lakshmi Vineela Nalla, Anil Dharavath, Amit Shard, Kiran Kalia, Amit Khairnar","doi":"10.1007/s12307-019-00226-0","DOIUrl":"10.1007/s12307-019-00226-0","url":null,"abstract":"Metabolic reprogramming is a newly emerged hallmark of cancer attaining a recent consideration as an essential factor for the progression and endurance of cancer cells. A prime event of this altered metabolism is increased glucose uptake and discharge of lactate into the cells surrounding constructing a favorable tumor niche. Several oncogenic factors help in promoting this consequence including, pyruvate kinase M2 (PKM2) a rate-limiting enzyme of glycolysis in tumor metabolism via exhibiting its low pyruvate kinase activity and nuclear moon-lightening functions to increase the synthesis of lactate and macromolecules for tumor proliferation. Not only its role in cancer cells but also its role in the tumor microenvironment cells has to be understood for developing the small molecules against it which is lacking with the literature till date. Therefore, in this present review, the role of PKM2 with respect to various tumor niche cells will be clarified. Further, it highlights the updated list of therapeutics targeting PKM2 pre-clinically and clinically with their added limitations. This upgraded understanding of PKM2 may provide a pace for the reader in developing chemotherapeutic strategies for better clinical survival with limited resistance.","PeriodicalId":9425,"journal":{"name":"Cancer Microenvironment","volume":"12 2-3","pages":"149-167"},"PeriodicalIF":0.0,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12307-019-00226-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37315656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 19

Immunosuppressive Tumor Microenvironment Status and Histological Grading of Endometrial Carcinoma. 子宫内膜癌免疫抑制肿瘤微环境状态及组织学分级。

Cancer Microenvironment Pub Date : 2019-12-01 Epub Date: 2019-05-27 DOI: 10.1007/s12307-019-00225-1

Julie Antomarchi, Damien Ambrosetti, Charlotte Cohen, Jérôme Delotte, Anne Chevallier, Babou Karimdjee-Soilihi, Mélanie Ngo-Mai, Annie Schmid-Alliana, Heidy Schmid-Antomarchi

{"title":"Immunosuppressive Tumor Microenvironment Status and Histological Grading of Endometrial Carcinoma.","authors":"Julie Antomarchi, Damien Ambrosetti, Charlotte Cohen, Jérôme Delotte, Anne Chevallier, Babou Karimdjee-Soilihi, Mélanie Ngo-Mai, Annie Schmid-Alliana, Heidy Schmid-Antomarchi","doi":"10.1007/s12307-019-00225-1","DOIUrl":"https://doi.org/10.1007/s12307-019-00225-1","url":null,"abstract":"The recent successes of new cancer immunotherapy approaches have led to investigate their relevance in the context of the Endometrial Carcinoma (EC). These therapies, that take the tumor-induced immunosuppressive microenvironment into account, target the tumor immune escape, in particular the inhibitory receptors involved in the regulation of the effector T cells' activity (immune checkpoints). The aim of this study was to identify, in ECs, differences in intergrades immune status that could contribute to the differences in tumor aggressiveness, and could also be used as theranostic tools. The immune status of tumors was assessed by quantitative real-time PCR. We analyzed the expression of specific genes associated to specific leukocytes subpopulations and the expression of reporting genes associated with the tumor escape/resistance. This study highlights significant differences in the EC intergrades immune status especially the tumor-infiltrating cell types and their activation status as well as in the molecular factors produced by the environment. The immune microenvironment of grade 1 ECs hints at a robust tumoricidal milieu while that of higher grades is more evocative of a tolerogenic milieu. This genes-based immunological monitoring of tumors that easily highlights significant intergrade differences relating to the density, composition and functional state of the leukocyte infiltrate, could give solid arguments for choosing the best therapeutic options, especially those targeting immune checkpoints. Moreover it could enable an easy adaptation of individual treatment approaches for each patient.","PeriodicalId":9425,"journal":{"name":"Cancer Microenvironment","volume":"12 2-3","pages":"169-179"},"PeriodicalIF":0.0,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12307-019-00225-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37282731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 20

Pleiotropic Effects of Epithelial Mesenchymal Crosstalk on Head and Neck Cancer: EMT and beyond. 上皮间充质串扰对头颈癌的多效性作用:EMT及其他。

Cancer Microenvironment Pub Date : 2019-12-01 Epub Date: 2019-07-11 DOI: 10.1007/s12307-019-00228-y

T B Steinbichler, D Savic, D Dejaco, A Romani, B Kofler, I I Skvortsova, H Riechelmann, J Dudas

{"title":"Pleiotropic Effects of Epithelial Mesenchymal Crosstalk on Head and Neck Cancer: EMT and beyond.","authors":"T B Steinbichler, D Savic, D Dejaco, A Romani, B Kofler, I I Skvortsova, H Riechelmann, J Dudas","doi":"10.1007/s12307-019-00228-y","DOIUrl":"10.1007/s12307-019-00228-y","url":null,"abstract":"Epithelial mesenchymal crosstalk (EMC) describes the interaction of the tumor stroma and associated fibroblasts with epithelial cancer cells. In this study we analysed the effects of EMC on head and neck cancer cells. In tumor cell lines EMC was induced using media conditioned from a mix-culture of cancer cells and fibroblasts. Cell proliferation and chemotherapy response were assessed using direct cell counting. Flow cytometry, immunohistochemistry of markers of epithelial-mesenchymal transition (EMT) and subsequent TissueFaxs™ acquisition and quantification and western blot analysis were performed. Holotomographic microscopy imaging was used to visualize the effects of EMC on Cisplatin response of SCC-25 cells. EMC induced a hybrid epithelial-mesenchymal phenotype in SCC-25 cells with co-expression of vimentin and cytokeratin. This hybrid phenotype was associated with chemotherapy resistance and increased proliferation of the cells. The EMC conditioned medium led to an activation of the IL-6/STAT3 pathway with subsequent phosphorylation of STAT3. EMC induced a hybrid epithelial-mesenchymal phenotype in HNSCC cells accompanied by increased therapy resistance and cell proliferation. The IL-6/STAT3 pathway might be one of the major pathways involved in these EMC-related effects.","PeriodicalId":9425,"journal":{"name":"Cancer Microenvironment","volume":"12 2-3","pages":"67-76"},"PeriodicalIF":0.0,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12307-019-00228-y","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37410282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 8

Ascites from Ovarian Cancer Induces Novel Fucosylated Proteins. 卵巢癌腹水诱导新的聚焦蛋白。

Cancer Microenvironment Pub Date : 2019-12-01 Epub Date: 2019-07-02 DOI: 10.1007/s12307-019-00227-z

Dulce Rosario Alberto-Aguilar, Verónica Ivonne Hernández-Ramírez, Juan Carlos Osorio-Trujillo, Dolores Gallardo-Rincón, Alfredo Toledo-Leyva, Patricia Talamás-Rohana

{"title":"Ascites from Ovarian Cancer Induces Novel Fucosylated Proteins.","authors":"Dulce Rosario Alberto-Aguilar, Verónica Ivonne Hernández-Ramírez, Juan Carlos Osorio-Trujillo, Dolores Gallardo-Rincón, Alfredo Toledo-Leyva, Patricia Talamás-Rohana","doi":"10.1007/s12307-019-00227-z","DOIUrl":"https://doi.org/10.1007/s12307-019-00227-z","url":null,"abstract":"Ovarian cancer is considered to be the most lethal type of gynecological cancer. During the advanced stages of ovarian cancer, an accumulation of ascites is observed. Fucosylation has been classified as an abnormal post-translational modification that is present in many diseases, including ovarian cancer. Ovarian cancer cells that are cultured with ascites stimulation change their morphology; concomitantly, the fucosylation process is altered. However, it is not known which fucosylated proteins are modified. The goal of this work was to identify the differentially fucosylated proteins that are expressed by ovarian cancer cell lines that are cultured with ovarian cancer patients' ascites. Aleuria aurantia lectin was used to detect fucosylation, and some changes were observed, especially in the cell membrane. Affinity chromatography and mass spectrometry (MALDI-TOF) were used to identify 6 fucosylated proteins. Four proteins (Intermediate filament family orphan 1 [IFFO1], PHD finger protein 20-like protein 1 [PHF20L1], immunoglobulin gamma 1 heavy chain variable region partial [IGHV1-2], and Zinc finger protein 224 [ZNF224]) were obtained from cell cultures stimulated with ascites, and the other two proteins (Peregrin [BRPF1] and Dystrobrevin alpha [DTNA]) were obtained under normal culture conditions. The fucosylated state of some of these proteins was further analyzed. The experimental results show that the ascites of ovarian cancer patients modulated the fucosylation process. The PHD finger protein 20-like protein 1, Zinc finger protein 224 and Peregrin proteins colocalize with fucosylation at different levels.","PeriodicalId":9425,"journal":{"name":"Cancer Microenvironment","volume":"12 2-3","pages":"181-195"},"PeriodicalIF":0.0,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12307-019-00227-z","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37385451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 6

The Cross Talk between Cancer Stem Cells/Cancer Initiating Cells and Tumor Microenvironment: The Missing Piece of the Puzzle for the Efficient Targeting of these Cells with Immunotherapy 肿瘤干细胞/肿瘤启动细胞与肿瘤微环境之间的串扰:免疫治疗有效靶向这些细胞的缺失部分

Cancer Microenvironment Pub Date : 2019-11-22 DOI: 10.1007/s12307-019-00233-1

Shilpa Ravindran, Saad Rasool, C. Maccalli

引用次数: 33

The Concomitant Expression of Human Endogenous Retroviruses and Embryonic Genes in Cancer Cells under Microenvironmental Changes is a Potential Target for Antiretroviral Drugs 微环境变化下人类内源性逆转录病毒和胚胎基因在癌细胞中的共同表达是抗逆转录病毒药物的潜在靶点

Cancer Microenvironment Pub Date : 2019-11-05 DOI: 10.1007/s12307-019-00231-3

Alessandro Giovinazzo, E. Balestrieri, Vita Petrone, Ayele Argaw-Denboba, C. Cipriani, M. Miele, S. Grelli, P. Sinibaldi‐Vallebona, C. Matteucci

引用次数: 7

Tumor-Infiltrating Immunosuppressive Cells in Cancer-Cell Plasticity, Tumor Progression and Therapy Response 肿瘤浸润性免疫抑制细胞在肿瘤细胞可塑性、肿瘤进展和治疗反应中的作用

Cancer Microenvironment Pub Date : 2019-10-03 DOI: 10.1007/s12307-019-00232-2

Laura Lorenzo-Sanz, P. Muñoz

引用次数: 40

Kinins in Glioblastoma Microenvironment 胶质母细胞瘤微环境中的激肽

Cancer Microenvironment Pub Date : 2019-08-16 DOI: 10.1007/s12307-019-00229-x

Mona N. Oliveira, B. Breznik, M. Pillat, Ricardo L. Pereira, H. Ulrich, T. Lah

引用次数: 9

Altered T Cell Migratory Capacity in the Progression from Barrett Oesophagus to Oesophageal Adenocarcinoma. Barrett食管向食管腺癌发展过程中T细胞迁移能力的改变。

Cancer Microenvironment Pub Date : 2019-04-01 Epub Date: 2019-03-04 DOI: 10.1007/s12307-019-00220-6

Maria E Kavanagh, Melissa J Conroy, Niamh E Clarke, Niamh T Gilmartin, Ronan Feighery, Finbar MacCarthy, Dermot O'Toole, Narayanasamy Ravi, John V Reynolds, Jacintha O' Sullivan, Joanne Lysaght

{"title":"Altered T Cell Migratory Capacity in the Progression from Barrett Oesophagus to Oesophageal Adenocarcinoma.","authors":"Maria E Kavanagh, Melissa J Conroy, Niamh E Clarke, Niamh T Gilmartin, Ronan Feighery, Finbar MacCarthy, Dermot O'Toole, Narayanasamy Ravi, John V Reynolds, Jacintha O' Sullivan, Joanne Lysaght","doi":"10.1007/s12307-019-00220-6","DOIUrl":"https://doi.org/10.1007/s12307-019-00220-6","url":null,"abstract":"Oesophageal adenocarcinoma (OAC) is an inflammation-driven cancer with poor prognosis and incidence is increasing rapidly. OAC arises from gastro-oesophageal reflux disease (GORD) and reflux-induced Barrett oesophagus (BO). The role of T cells in this disease progression is not yet fully understood. We have previously demonstrated higher proportions of pro-tumour Th2 cells in BO tissue, implicating them in its pathogenesis. While a Th2 immune profile is thought to underlie the metaplastic transformation in BO and promote OAC development, our studies suggest that the abundance of Th2 cells in BO tissue is likely to occur through altered T cell recruitment. This study examined the chemokine networks governing T cell migration to oesophageal tissue during disease progression. Here, we have identified that circulating T cells in OAC patients, exhibit impaired migratory capacity with decreased frequencies of Th1-associated CXCR3+ and Th17-associated CCR6+ cells. Despite the abundance of Th1 chemokines RANTES (CCL5) and MIP-1α (CCL3) in OAC tumour, enrichments of intratumoural T cells expressing corresponding receptors were not observed. These data suggest that T cell infiltration of oesophageal tissue is compromised in OAC and suggest that future therapies targeting T cell trafficking should occur at the pre-neoplastic stage. This is supported by the finding that antagonism of Th2-biased CCR4 significantly reduces T cell migration in BO but not OAC patients. Since we have previously reported a predominant Th2 immune profile in BO, we suggest that chemokine receptor antagonism may be a viable treatment option to alleviate Th2-predominance in BO and interrupt progression to OAC.","PeriodicalId":9425,"journal":{"name":"Cancer Microenvironment","volume":"12 1","pages":"57-66"},"PeriodicalIF":0.0,"publicationDate":"2019-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12307-019-00220-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37024008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 17

The Tumor Microenvironment in Post-Transplant Lymphoproliferative Disorders. 移植后淋巴细胞增生性疾病的肿瘤微环境。

Cancer Microenvironment Pub Date : 2019-04-01 Epub Date: 2019-01-24 DOI: 10.1007/s12307-018-00219-5

Lukas Marcelis, Thomas Tousseyn

{"title":"The Tumor Microenvironment in Post-Transplant Lymphoproliferative Disorders.","authors":"Lukas Marcelis, Thomas Tousseyn","doi":"10.1007/s12307-018-00219-5","DOIUrl":"https://doi.org/10.1007/s12307-018-00219-5","url":null,"abstract":"Post-transplant lymphoproliferative disorders (PTLDs) cover a broad spectrum of lymphoproliferative lesions arising after solid organ or allogeneic hematopoietic stem cell transplantation. The composition and function of the tumor microenvironment (TME), consisting of all non-malignant constituents of a tumor, is greatly impacted in PTLD through a complex interplay between 4 factors: 1) the graft organ causes immune stimulation through chronic antigen presentation; 2) the therapy to prevent organ rejection interferes with the immune system; 3) the oncogenic Epstein-Barr virus (EBV), present in 80% of PTLDs, has a causative role in the oncogenic transformation of lymphocytes and influences immune responses; 4) interaction with the donor-derived immune cells accompanying the graft. These factors make PTLDs an interesting model to look at cancer-microenvironment interactions and current findings can be of interest for other malignancies including solid tumors. Here we will review the current knowledge of the TME composition in PTLD with a focus on the different factors involved in PTLD development.","PeriodicalId":9425,"journal":{"name":"Cancer Microenvironment","volume":"12 1","pages":"3-16"},"PeriodicalIF":0.0,"publicationDate":"2019-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12307-018-00219-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36939643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 17