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      The immune infiltration in clear cell Renal Cell Carcinoma and their clinical implications: A study based on TCGA and GEO databases

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          Abstract

          The tumor immune microenvironment in clear cell Renal Cell Carcinoma (ccRCC) still remains poorly understood. Previous methods to study the tumor immune microenvironment have a limitation when accounting for the functionally distinct cell types. In this study, we investigated the differently infiltrated immune cells and their clinical significance in ccRCC for the purpose of shedding some important light on the complex immune microenvironment in ccRCC. The devolution algorithm (CIBERSORT) was applied to infer the proportion of 22 immune infiltrating cells based on gene expression profiles of ccRCC bulk tissue, which were downloaded from TCGA and GEO databases. As a result, we observed considerable differences in immune cells percentage between ccRCC tumor tissue and paired normal tissue; meanwhile, we uncovered their internal correlations and associations with Fuhrman grade. Moreover, dendritic cells resting, dendritic cells activated, mast cells resting, mast cells activated and eosinophils were associated with favorable prognosis, whereas B cells memory, T cells follicular helper and T cells regulatory (Tregs) were correlated with poorer outcome.

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          Most cited references20

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          Cancer immunotherapy: harnessing the immune system to battle cancer.

          The recent clinical successes of immune checkpoint blockade and chimeric antigen receptor T cell therapies represent a turning point in cancer immunotherapy. These successes also underscore the importance of understanding basic tumor immunology for successful clinical translation in treating patients with cancer. The Reviews in this Review Series focus on current developments in cancer immunotherapy, highlight recent advances in our understanding of basic aspects of tumor immunology, and suggest how these insights can lead to the development of new immunotherapeutic strategies.
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            Neutrophil: A Cell with Many Roles in Inflammation or Several Cell Types?

            Neutrophils are the most abundant leukocytes in the circulation, and have been regarded as first line of defense in the innate arm of the immune system. They capture and destroy invading microorganisms, through phagocytosis and intracellular degradation, release of granules, and formation of neutrophil extracellular traps after detecting pathogens. Neutrophils also participate as mediators of inflammation. The classical view for these leukocytes is that neutrophils constitute a homogenous population of terminally differentiated cells with a unique function. However, evidence accumulated in recent years, has revealed that neutrophils present a large phenotypic heterogeneity and functional versatility, which place neutrophils as important modulators of both inflammation and immune responses. Indeed, the roles played by neutrophils in homeostatic conditions as well as in pathological inflammation and immune processes are the focus of a renovated interest in neutrophil biology. In this review, I present the concept of neutrophil phenotypic and functional heterogeneity and describe several neutrophil subpopulations reported to date. I also discuss the role these subpopulations seem to play in homeostasis and disease.
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              Proliferative activity of intratumoral CD8(+) T-lymphocytes as a prognostic factor in human renal cell carcinoma: clinicopathologic demonstration of antitumor immunity.

              Tumor-infiltrating lymphocytes, particularly CD8(+) T cells, could be a manifestation of antitumor immunity. We clinicopathologically analyzed the biological significance of tumor-infiltrating lymphocytes in 221 patients with renal cell carcinoma without preoperative treatments. More abundant infiltration of tumor tissue not only by CD8(+) but also CD4(+) T cells was associated with shorter survival of the patients, because of the positive correlation between the number of lymphocytes and representative tumor grade factors. This suggests that immune cell reactions are more pronounced as the tumor grade/biological malignancy progresses, probably because of increased antigenicity of tumor cells. We next analyzed the proliferative activity of CD8(+) T cells that infiltrated in tumor cell nests, which could also reflect antitumor immunity. Higher labeling index of Ki-67, a proliferation-associated antigen, among CD8(+) T cells in contact to tumor cells was associated with a longer survival by both uni- and multivariate analyses. Our data in human renal cell carcinoma suggest that infiltration of tumor tissue by T cells itself does not denote the efficacy of antitumor immunity because of its dependence on the biological malignancy of tumor cells, but infiltration of tumor tissue by CD8(+) T cells bearing more pronounced proliferative activity could reflect effective antitumor immunity. This concept would be important for future immunotherapy of human cancer.
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                Author and article information

                Journal
                J Cancer
                J Cancer
                jca
                Journal of Cancer
                Ivyspring International Publisher (Sydney )
                1837-9664
                2020
                5 March 2020
                : 11
                : 11
                : 3207-3215
                Affiliations
                [1 ]Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
                [2 ]Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, China.
                Author notes
                ✉ Corresponding author: Professor Bing Li, Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. E-mail: bingli@ 123456hust.edu.cn .; Tel: +86 27 85351625 Fax: +86 27 85726970

                *Equal contributions to this study.

                Competing Interests: The authors have declared that no competing interest exists.

                Article
                jcav11p3207
                10.7150/jca.37285
                7097965
                32231726
                fc5338d6-bdb4-4a44-9b09-9a06f3a3ae6d
                © The author(s)

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.

                History
                : 3 June 2019
                : 5 February 2020
                Categories
                Research Paper

                Oncology & Radiotherapy
                devolution algorithm,tumor microenvionment,clear cell renal cell carcinoma (ccrcc),genomic signature

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