B cells are associated with survival and immunotherapy response in sarcoma

Petitprez, Florent; Reyniès, Aurélien de; Keung, Emily Z.; Chen, Tom Wei‐Wu; Sun, Chengming; Caldéraro, Julien; Jeng, Yung‐Ming; Hsiao, Li-Ping; Lacroix, Laetitia; Bougoüin, Antoine; Moreira, Marco; Lacroix, Guillaume; Natario, Ivo; Adam, Julien; Lucchesi, Carlo; Laizet, Yec’han; Toulmonde, Maud; Burgess, Melissa; Bolejack, Vanessa; Reinke, Denise K.; Wani, Khalid M.; Wang, Wei‐Lien; Lazar, Alexander J.; Roland, Christina L.; Wargo, Jennifer A.; Italiano, Antoîne; Fridman, Wolf‐Herman; Tawbi, Hussein A.; Fridman, Wolf Herman

doi:10.1038/s41586-019-1906-8

Cited by 1,402 publications

(1,303 citation statements)

References 39 publications

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“…CD20 is a 33-37 kDa transmembrane phosphoprotein, which is expressed on B-lymphocyte precursors and mature B-lymphocytes. CD20 positive B-cell infiltration has been associated with improved patient survival as well as increased immunotherapy response in various cancers [23,24]. Until now, there were only two studies investigating the association of CD20-positive B-cells with survival in patients with pancreatic carcinomas.…”

Section: Discussionmentioning

confidence: 99%

Upregulation of CD20 Positive B-Cells and B-Cell Aggregates in the Tumor Infiltration Zone is Associated with Better Survival of Patients with Pancreatic Ductal Adenocarcinoma

Brunner

Maier

Rümmele

et al. 2020

IJMS

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Patients with pancreatic ductal adenocarcinoma (PDAC) normally have a poor long-term prognosis. However, some rare cases of long-term survivors have been reported. The tumor microenvironment, consisting of cellular and stromal components, possibly plays an important role and might influence prognosis. In this context, the role of tumor-infiltrating B-cells and its impact on the survival in patients with PDAC remains controversial. We therefore aimed to assess the prognostic value of CD20-positive B-cells and CD20-positive B-cell aggregates as well as CD138, IgM, Pax5, and Ki67 on the survival of patients with PDAC using immunohistochemistry of FFPE pancreatectomy tissue sections from patients that underwent primary surgery for pT3and R0-pancreatic adenocarcinoma between 1995 and 2016. Patients with PDAC were matched and grouped in 16 long-term-survivors (LTS, median overall survival (OS): 96 months [range: 61-177 months]) and 16 short-term-survivors (STS, median OS: 16 months [range: 7-32 months]). CD20-positive B-cells and B-cell aggregates in the tumor infiltration zone were significantly upregulated in the LTS-group compared to the STS-group (p = 0.0499 respectively p = 0.0432). Regarding the entire patient cohort (n = 32) CD20 positive B-cell aggregates in the tumor infiltration zone were an independent prognostic marker for overall survival in multivariate analysis (HR 9.2, CI 1.6-51.4, p = 0.012). These results underline the importance of tumor-associated B-cells for prognosis of patients with PDAC. The detailed role of B cells in the pathomechanism of PDAC should be further investigated for predicting outcome, identifying appropriate treatment regimens, and developing novel therapeutic options. and 10-year survival rates are low, ranging in Germany from 4% to 17% and 2% to 12%, respectively [3]. Although progress has been made in multimodal treatment approaches, the mortality rate of PDAC is still increasing throughout the years. Surgery is considered the only potential curative treatment for PDAC but is reserved for the minority of patients with non-metastatic and locally resectable tumors. Most patients with PDAC remain asymptomatic until the disease develops to an advanced inoperable stage, leading to its disappointing prognosis [4].The determination of prognostic factors in patients with PDAC is essential for predicting the outcome and for identifying appropriate treatment strategies. Known clinical prognostic parameters include age, tumor stage, lymph node status, grading, perineural invasion, and for resected patients' resection status, adjuvant chemotherapy and hospital volume [5][6][7].Moreover, it has long been recognized that the tumor microenvironment and an involvement of the immune system play a distinctive role in the biological behavior of cancer [8]. PDACs are characterized by an immunosuppressive microenvironment due to the dysfunction of the immune system, which is a result of the involvement of multiple types of immune cells, including cancer-associated fibroblasts, regulatory T cells, m...

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Section: Discussionmentioning

confidence: 99%

Upregulation of CD20 Positive B-Cells and B-Cell Aggregates in the Tumor Infiltration Zone is Associated with Better Survival of Patients with Pancreatic Ductal Adenocarcinoma

Brunner

Maier

Rümmele

et al. 2020

IJMS

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“…The presence of B cells in tertiary lymphoid structures (TLSs) in tumors predicts the outcome of checkpoint blockade immunotherapy, a trio of studies suggest. [3][4][5] Using samples from patients with melanoma and sarcoma, the researchers also showed that tumors that respond better to immunotherapy are more likely to develop TLSs in the course of treatment, indicating that B cells might play a role in antitumor immunity.…”

Section: Intratumoral B Cells Mark Better Response To Immunotherapymentioning

confidence: 99%

Human Vaccines & Immunotherapeutics: news

2020

Human Vaccines & Immunotherapeutics

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“…The number of differently expressed RNA varied across tumor types (ranging from 406 to 1308, <1000 in BRCA, COAD, HNSC, LIHC, LUAD, LUSC, PRAD, READ, SKCM, >1000 in BLCA, STAD). Among them, down-regulated mRNA (inflamed tumor-specific) represents the most striking signatures that account for major differences between inflamed TME and non-inflamed TME ( Figure. Translocation-Associated Protein 2 (FCRL5), suggesting inflamed tumor types were also B-cell rich tumor, which has been proven as a key factor determining the sensitivity for immunotherapy [15,16].…”

Section: Figure1 Umap Dimension Plot Of Cells In Tumors Each Dot Rementioning

confidence: 99%

Pan-cancer analysis identified inflamed microenvironment associated multi-omics signatures

Wang

Liu

Ran

et al. 2020

Preprint

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BackgroundImmunotherapy has revolutionized cancer therapy. However, responses are not universal. The inflamed tumor microenvironment has been reported to correlate with response in tumor patients. However, how different tumors shape their tumor microenvironment remains a critical unsolved problem. A deeper insight into the molecular characteristics of inflamed tumor microenvironment may be needed. Materials and methodsHere, based on single-cell RNA sequencing technology and TCGA pan-cancer cohort, we investigated multi-omics molecular features of tumor microenvironment phenotypes. Based on single-cell RNA-seq analysis, we classified pan-cancer tumor samples into inflamed or noninflamed tumor and identified molecular features of these tumors. Analysis of integrating identified gene signatures with a drug-genomic perturbation database identified multiple drugs which may be helpful for converting non-inflamed tumors to inflamed tumors. ResultsOur results revealed several inflamed/non-inflamed tumor microenvironments-specific molecular characteristics. For example, inflamed tumors highly expressed miR-650 and lncRNA including MIR155HG and LINC00426, these tumors showed activated cytokines-related signaling pathways. Interestingly, non-inflamed tumors tended to express several genes related to neurogenesis. Multiomics analysis demonstrated the neuro phenotype transformation may be induced by hypomethylated promoters of these genes and down-regulated miR-650. Drug discovery analysis revealed histone deacetylase inhibitors may be a potential choice for helping favorable tumor microenvironment phenotype transformation and aiding current immunotherapy. ConclusionOur results provide a comprehensive molecular-level understanding of tumor cell-immune cell interaction and may have profound clinical implications.

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B cells are associated with survival and immunotherapy response in sarcoma

Cited by 1,402 publications

References 39 publications

Upregulation of CD20 Positive B-Cells and B-Cell Aggregates in the Tumor Infiltration Zone is Associated with Better Survival of Patients with Pancreatic Ductal Adenocarcinoma

Upregulation of CD20 Positive B-Cells and B-Cell Aggregates in the Tumor Infiltration Zone is Associated with Better Survival of Patients with Pancreatic Ductal Adenocarcinoma

Human Vaccines & Immunotherapeutics: news

Pan-cancer analysis identified inflamed microenvironment associated multi-omics signatures

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