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

[Tertiary lymphoid structures generate and propagate anti-tumor antibody-producing plasma cells in renal cell cancer].

Un procedimiento in vitro para el pronostico del tiempo de supervivencia de un paciente que padece un cancer, en el que dicho procedimiento es mediante la medicion del nivel de la respuesta inmune adaptativa de dicho paciente, en el que una respuesta inmune adaptativa fuerte se correlaciona con un pronostico del cancer favorable y una respuesta inmune adaptativa debil se correlaciona con un pronostico pobre y en el que dicho procedimiento comprende las etapas siguientes: a. llevar a cabo una cuantificacion de la densidad celular de celulas CD45RO+ en muestras de tejido tumoral recogidas de dos regiones separadas del tumor de dicho paciente, respectivamente (i) el centro del tumor (CT) y (ii) el borde invasivo del tumor (IM), y b. llevar a cabo las etapas de comparacion siguientes: i. comparar el valor de cuantificacion obtenido en la etapa a) para celulas CD45RO+ en CT con un valor de referencia CT predeterminado para celulas CD45RO+, y ii. comparar el valor de cuantificacion obtenido en la etapa a) para celulas CD45RO+ en IM con un valor de referencia IM predeterminado para celulas CD45RO+, y en el que cuando el valor de cuantificacion obtenido en la etapa a) para celulas CD45RO+ en CT es mayor que el valor de referencia CT predeterminado para celulas CD45RO+ y el valor de cuantificacion obtenido en la etapa a) para celulas CD45RO+ en IM es mayor que el valor de referencia IM predeterminado para celulas CD45RO+, entonces se determina un pronostico de resultado favorable para dicho cancer y cuando el valor de cuantificacion obtenido en la etapa a) para celulas CD45RO+ en CT es menor que el valor de referencia CT predeterminado para celulas CD45RO+ y el valor de cuantificacion obtenido en la etapa a) para celulas CD45RO+ en IM es menor que el valor de referencia IM predeterminado para celulas CD45RO+, entonces se determina un pronostico de resultado pobre para dicho cancer.

An in vitro method for the prognosis of progression of a cancer using CD45 as a marker

P214 - Expression et fonction de l’il-17 dans les lymphomes T cutanés


 The presence of tertiary lymphoid structures (TLSs) and a high intratumoral density of B lymphocytes have been associated with improved survival in several tumor types. We investigated the impact of TLS on responses to immunotherapy and, analyzing a large-scale retrospective analysis of three independent cohorts of patients with cancer, including sarcomas, who were treated with anti-PD-1 or anti-PD-L1 antibodies, we showed that the presence of mature TLSs was associated with improved objective response rates, progression-free survival and overall survival, independent of PD-L1 expression status and CD8+T cell density. To decipher the role of B cells in such responses, we performed spatial transcriptomics and examined the nature of B cell responses within TLS structure. B cells were enriched in TLS, and therein we could identify all B cell maturation stages toward plasma cell (PC) formation. B cell repertoire analysis revealed clonal diversification, selection, expansion in TLS and the presence of full mature clonotypes at distance. In TLS+ tumors, IgG producing PCs disseminated into the tumor beds along fibroblastic tracks. TLS+ tumors exhibited high frequencies of IgG-producing PCs and IgG-stained and apoptic malignant cells, suggestive of anti-tumor effector activity. We validated these findings in a prospective trial in metastatic Soft Tissue Sarcoma (STS) bearing patients. PEMBROSARC is a multi-cohort phase II study of pembrolizumab combined with low-dose cyclophosphamide in patients with advanced STS. The 6-months non-progressive rate (NPR) and the objective response rates previously reported in cohorts including all comers were 4.9% and 2.4%, respectively. In the cohort enrolling patients selected based on the presence of TLS, the 6-month NPR was 40% and the objective response rate was 30%. Exploratory analyses reveled that infiltration by IgG antibody-producing plasma cells was associated with improved clinical outcome as well as the presence of IgG antibodies on tumor cells. Altogether, these results establish that maturation, selection and amplification of B cells in intratumoral TLSs results in Plasma Cells generation which may produce anti-tumor antibodies. The latter may amplify in situ antitumor immune responses leading to better therapeutic responses to immunotherapy.
 Citation Format: Wolf H. Fridman. B cell immunity generation in tertiary lymphoid structures, a major determinant of sarcoma immune response to immunotherapy [abstract]. In: Proceedings of the AACR Special Conference: Sarcomas; 2022 May 9-12; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2022;28(18_Suppl):Abstract nr IA007.

Abstract IA007: B cell immunity generation in tertiary lymphoid structures, a major determinant of sarcoma immune response to immunotherapy

In-vitro-verfahren zur prognose des fortschreitens einer krebserkrankung und des ausgangs für einen patienten sowie verfahren zur durchführung des verfahrens

Wolf H. Fridman

Papers

[Tertiary lymphoid structures generate and propagate anti-tumor antibody-producing plasma cells in renal cell cancer].

An in vitro method for the prognosis of progression of a cancer using CD45 as a marker

P214 - Expression et fonction de l’il-17 dans les lymphomes T cutanés

Abstract IA007: B cell immunity generation in tertiary lymphoid structures, a major determinant of sarcoma immune response to immunotherapy

In-vitro-verfahren zur prognose des fortschreitens einer krebserkrankung und des ausgangs für einen patienten sowie verfahren zur durchführung des verfahrens