https://cancerbiologyprogram.med.wayne.edu/pdfs/hallmarks_cancer_article.pdf

Hallmarks of cancer: the next generation.

There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Increasing quantitative data generated from transcriptomics and proteomics require integrative strategies for analysis Here, we present an R package, clusterProfiler that automates the process of biological-term classification and the enrichment analysis of gene clusters The analysis module and visualization module were combined into a reusable workflow Currently, clusterProfiler supports three species, including humans, mice, and yeast Methods provided in this package can be easily extended to other species and ontologies The clusterProfiler package is released under Artistic-20 License within Bioconductor project The source code and vignette are freely available at http://bioconductororg/packages/release/bioc/html/clusterProfilerhtml

/pdf/clusterprofiler-an-r-package-for-comparing-biological-themes-xbzzr3fbnj.pdf

clusterProfiler: an R Package for Comparing Biological Themes Among Gene Clusters

http://aiocm.org/member/Immunity,%20Inflammation,%20and%20Cancer.pdf

Immunity, Inflammation, and Cancer

Resume Dans des modeles precliniques et dans certains cancers les lymphocytes T specifiques d’antigenes de tumeurs jouent un role important dans le controle de la proliferation des tumeurs. Neanmoins, dans de nombreuses situations tumorales, leur presence ne semble pas influer sur la progression de la tumeur. Une meilleure analyse de l’heterogeneite phenotypique et fonctionnelle de ces lymphocytes T au contact des tumeurs et des mecanismes de resistance a l’action cytotoxique de ces cellules developpes par la tumeur permettraient d’optimiser les traitements d’immunotherapie anti-tumorale.

Phénotypes et fonctions des lymphocytes T en pathologie tumorale

Antigen-stimulated T lymphocytes release a variety of soluble factors among which an Immunoglobulin Binding Factor (IBF). We report a method of titration of IBF making use of its capacity to inhibit complement-dependent hemolysis of sheep erythrocytes sensitized with rabbit IgG antibodies. Using this technique we have investigated the specificity of IBG for rabbit immunoglobulins fractionated by DEAE-cellulose chromatography. The interaction of IBF with IgG is found to be restricted to the slowest migrating fractions of rabbit IgG.

Immunoglobulin binding factor (IBF) produced by T cells: selective interaction with slow migrating rabbit IgC.

Caractérisation de l'infiltrat des mélanomes malins humains d'après la nature des rĕcepteurs de surface. II. -- ĕtude sur cellules extraites de la tumeur

Although many human cancers are located in mucosal sites, most cancer vaccines are tested against subcutaneous tumors in preclinical models. The utility of preferentially inducing an anti-tumor immune response in the mucosal anatomic site of tumors has never been addressed. We therefore wondered whether mucosa-specific homing instructions to the immune system might influence mucosal tumor outgrowth. For this purpose, we set up original orthotopic models of head and neck and lung cancers monitored by magnetic resonance imaging or luciferase based in vivo optical imaging and vaccine based on a non replicative delivery system, the B subunit of Shiga toxin (STxB) as mucosal vector which has previously been shown to target antigen to dendritic cells. We showed that the growth of orthotopic head and neck or lung cancers expressing the E7 protein from HPV16 was only inhibited, when a cancer vaccine was delivered by the intranasal (i.n) mucosal and not the intramuscular (i.m) route. This anti-tumor effect was dependent on mucosal CD8+T cells as : i) Only a vaccine composed of STxB coupled to an E7 derived polypeptide (STxB-E7), but not the free E7 polypeptide elicited mucosal CD8+T cells. This mucosal induction of anti-E7 CD8+T cells, but not the systemic (spleen) specific anti-E7 CD8+T cells correlated with mucosal tumor protection. ii) A greater mucosal tumor infiltration of CD8+T cells was detected 7 days after tumor graft in mice that had been previously intranasally immunized with STxB-E7, than in mice vaccinated by the i.m. route. iii) CD8+T cell-depleted mice vaccinated with STxB-E7 by the i.n. route died before 20 days, whereas mice survived more than 6 months without CD8 depletion. As control, both routes of vaccine administration controlled the growth of subcutaneous tumors and elicited anti-E7 specific CD8+T cells in the spleen. To explain this finding, we demonstrated that only i.n. vaccination elicited mucosal specific CD8+T cells expressing the mucosal integrin CD49a. Blockade of CD49a decreased intratumoral CD8+T cell infiltration and the efficacy of cancer vaccine on mucosal tumor. We then showed that after intranasal vaccination, only dendritic cell from lung parenchyma, but not from spleen induced the expression of CD49a on co-cultured specific CD8+T cells. Tumor-infiltrating lymphocytes from human mucosal lung cancer also expressed CD49a at higher levels than TIL from non mucosal tumors, supporting the relevance and possible extrapolation of these results in humans. We thus identified a link between the route of vaccination and the induction of a mucosal homing program on induced CD8+T cells controlling their trafficking with a direct application on the efficacy of cancer vaccine to control mucosal tumors. Citation Format: Federico Sandoval, Mevyn Nizard, Magali Terme, Cecile Badoual, Michel-Francis Bureau, Olivier Clement, Elie Marcheteau, Alain Gey, Estelle Dransart, Francoise Quintin-Colonna, Gwenhael Autret, Tzyy-Choou Wu, Wolf H. Fridman, Ludger Johannes, Eric Tartour. Mucosal imprinting of vaccine induced-CD8+T cells is crucial to inhibit mucosal tumors. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2830. doi:10.1158/1538-7445.AM2013-2830

Wolf H. Fridman

Papers

Phénotypes et fonctions des lymphocytes T en pathologie tumorale

Immunoglobulin binding factor (IBF) produced by T cells: selective interaction with slow migrating rabbit IgC.

Caractérisation de l'infiltrat des mélanomes malins humains d'après la nature des rĕcepteurs de surface. II. -- ĕtude sur cellules extraites de la tumeur

Abstract 2830: Mucosal imprinting of vaccine induced-CD8+T cells is crucial to inhibit mucosal tumors.

Towards a second century