Tumor-infiltrating B cells signal functional humoral immune responses in breast cancer

Garaud, Soizic; Buisseret, Laurence; Solinas, Cinzia; Gu-Trantien, Chunyan; Wind, Alexandre de; Eynden, Gert Van den; Naveaux, Céline; Lodewyckx, Jean-Nicolas; Boisson, Anaïs; Duvillier, Hughes; Craciun, Ligia; Ameye, Lieveke; Veys, Isabelle; Paesmans, Marianne; Larsimont, Denis; Piccart‐Gebhart, Martine; Willard-Gallo, Karen

doi:10.1172/jci.insight.129641

Cited by 218 publications

(185 citation statements)

References 80 publications

(118 reference statements)

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“…On the other hand, vimentin detection confirmed the presence of stromal cells. CD45, also known as leucocyte common antigen, is a transmembrane glycoprotein present in all nucleated cells of the hematopoietic lineage [ 28 ] and has been broadly used to assess immune cell population presence in breast tissue, such as tumor-infiltrating lymphocytes [ 29 – 31 ]. CD45 + cells were detected in 5 out of the 8 cases which presented immune cells in the original tissue (Fig.…”

Section: Resultsmentioning

confidence: 99%

A novel culture method that sustains ERα signaling in human breast cancer tissue microstructures

Cartaxo

Estrada

Domenici

et al. 2020

J Exp Clin Cancer Res

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Background: Estrogen receptor α (ERα) signaling is a defining and driving event in most breast cancers; ERα is detected in malignant epithelial cells of 75% of all breast cancers (classified as ER-positive breast cancer) and, in these cases, ERα targeting is the main therapeutic strategy. However, the biological determinants of ERα heterogeneity and the mechanisms underlying therapeutic resistance are still elusive, hampered by the challenges in developing experimental models recapitulative of intra-tumoral heterogeneity and in which ERα signaling is sustained. Ex vivo cultures of human breast cancer tissue have been proposed to retain the original tissue architecture, epithelial and stromal cell components and ERα. However, loss of cellularity, viability and ERα expression are well-known culture-related phenomena. Methods: BC samples were collected and brought to the laboratory. Then they were minced, enzymatically digested, entrapped in alginate and cultured for 1 month. The histological architecture, cellular composition and cell proliferation of tissue microstructures were assessed by immunohistochemistry. Cell viability was assessed by measurement of cell metabolic activity and histological evaluation. The presence of ERα was accessed by immunohistochemistry and RT-qPCR and its functionality evaluated by challenge with 17-β-estradiol and fulvestrant. Results: We describe a strategy based on entrapment of breast cancer tissue microstructures in alginate capsules and their long-term culture under agitation, successfully applied to tissue obtained from 63 breast cancer patients. After 1 month in culture, the architectural features of the encapsulated tissue microstructures were similar to the original patient tumors: epithelial, stromal and endothelial compartments were maintained, with an average of 97% of cell viability compared to day 0. In ERα-positive cases, fibers of collagen, the main extracellular matrix component in vivo, were preserved. ERα expression was at least partially retained at gene and protein levels and response to ERα stimulation and inhibition was observed at the level of downstream targets, demonstrating active ER signaling.

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Section: Resultsmentioning

confidence: 99%

A novel culture method that sustains ERα signaling in human breast cancer tissue microstructures

Cartaxo

Estrada

Domenici

et al. 2020

J Exp Clin Cancer Res

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“…In recent years, signi cant evidence has been found indicating that TICs in the tumor microenvironment (TME) play essential roles in the regulation of malignance and improvement of clinical outcomes in many tumors [10][11][12]. In particular, CD4+ and CD8+ T cells, regulatory T-cells (Tregs), dendritic cells (DCs), and macrophages appear to be highly predictive of patient outcome [13][14][15].…”

Section: Backgroudmentioning

confidence: 99%

WITHDRAWN: PLK1 is a Potential Prognostic Factor Associated With the Tumor Microenvironment During Lung Adenocarcinoma Progression

Huang¹,

Li²

2020

Preprint

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Background: Lung adenocarcinoma (LUAD) accounts for more than 40% of lung cancer cases worldwide, and the 5-year survival rate of LUAD patients is less than 10% due to a lack of reliable therapeutics. Here, we sought to identify a new therapeutic target for LUAD via bioinformatics analysis.Methods: Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was conducted for the differentially expressed genes (DEGs) identified in 551 samples from the Cancer Genome Atlas (TCGA) database. Gene set variation analysis (GSVA) and the CIBERSORT method were performed to estimate the expression profile of biological pathways and the population of tumor-infiltrating immune cells (TICs) in the TCGA dataset. DEGs were further analyzed by protein-protein interaction (PPI) network and Cox regression analyses, followed by RT-PCR and western blotting for confirmation. Results: Cell cycle was the only shared pathway identified by the KEGG and GSVA interaction analyses. Cell cycle score was positively associated with clinical characteristics (age, clinical stage, and metastasis) and negatively associated with overall survival in LUAD patients. PPI and Cox analyses identified PLK1 as a prognostic factor, which was positively correlated with clinical stage and negatively correlated with overall survival in LUAD patients. CIBERSORT analysis indicated that PLK1 expression was significantly positively correlated with CD8+ and activated memory CD4+ T cells, and negatively correlated with activated natural killer cells. Additionally, PLK1 overexpression resulted in increased immune cytotoxic metrics, such as cytolytic activity score, IFN-γ score, and IFN-γ level.Conclusions: PLK1 may be useful for survival estimation in LUAD patients due to its strong correlation with features of TICs in the tumor immune microenvironment.

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“…Elevated TIL scores were proven to correlate with increased pathological complete response to neoadjuvant chemotherapy. [44][45][46][47] This proves that the immune system plays a pivotal role in this subgroup of patients.…”

Section: Checkpoint Inhibition In Triple-negative Breast Cancermentioning

confidence: 74%

<p>Immunotherapy for the Treatment of Breast Cancer: Emerging New Data</p>

Mina

Lim

Bahadur

et al. 2020

BCTT

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Breast cancer is the most common type of cancer affecting women in the United States. Triple-negative breast cancer remains the most aggressive molecular subtype secondary to a lack of therapeutic targets. The search for a target has led us to investigate immunotherapeutic agents. Immunotherapy has recently demonstrated significant breakthroughs in various types of cancers that are refractory to traditional therapies including melanoma and Non-Small Cell Lung Cancer (NSCLC). Breast cancer however remains one of the tumors that was initially least investigated because of being considered to have a low immunogenic potential and a low mutational load. Over the past few years, antiPD1/PDL1 drugs have started to make progress in the triple-negative subtype with more promising outcomes. In this report, we review the treatment of triple-negative breast cancer and specifically shed light on advances in immunotherapy and newly approved drugs in this challenging disease.

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Tumor-infiltrating B cells signal functional humoral immune responses in breast cancer

Cited by 218 publications

References 80 publications

A novel culture method that sustains ERα signaling in human breast cancer tissue microstructures

A novel culture method that sustains ERα signaling in human breast cancer tissue microstructures

WITHDRAWN: PLK1 is a Potential Prognostic Factor Associated With the Tumor Microenvironment During Lung Adenocarcinoma Progression

<p>Immunotherapy for the Treatment of Breast Cancer: Emerging New Data</p>

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Tumor-infiltrating B cells signal functional humoral immune responses in breast cancer

Cited by 218 publications

References 80 publications

A novel culture method that sustains ERα signaling in human breast cancer tissue microstructures

A novel culture method that sustains ERα signaling in human breast cancer tissue microstructures

WITHDRAWN: PLK1&nbsp;is a Potential Prognostic Factor Associated With the Tumor Microenvironment During Lung Adenocarcinoma Progression

<p>Immunotherapy for the Treatment of Breast Cancer: Emerging New Data</p>

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WITHDRAWN: PLK1 is a Potential Prognostic Factor Associated With the Tumor Microenvironment During Lung Adenocarcinoma Progression