scholarly journals Intratumoral, rather than stromal, CD8+ T cells could be a potential negative prognostic marker in invasive breast cancer patients

2019 ◽  
Vol 12 (3) ◽  
pp. 585-595 ◽  
Author(s):  
Ivana Catacchio ◽  
Nicola Silvestris ◽  
Emanuela Scarpi ◽  
Laura Schirosi ◽  
Anna Scattone ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Cancer Patients ◽  
Prognostic Marker ◽  
Cd8 T Cells ◽  
Invasive Breast Cancer ◽  
Breast Cancer Patients

scholarly journals Resident memory CD8+ T cells within cancer islands mediate survival in breast cancer patients

JCI Insight ◽  
2019 ◽  
Vol 4 (19) ◽  
Author(s):  
Colt A. Egelston ◽  
Christian Avalos ◽  
Travis Y. Tu ◽  
Anthony Rosario ◽  
Roger Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Cancer Patients ◽  
Cd8 T Cells ◽  
Breast Cancer Patients ◽  
Memory Cd8 T Cells

scholarly journals 323 Systemic administration of ladiratuzumab vedotin alone or in combination with pembrolizumab results in significant immune activation in the tumor microenvironment in metastatic breast cancer patients

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A349-A349
Author(s):  
Lajos Pusztai ◽  
Hailing Lu ◽  
Christopher Hale ◽  
Anne Grosse-Wilde ◽  
Jennifer Specht ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Immune Response ◽  
T Cells ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Cd8 T Cells ◽  
Immune Activation ◽  
Metastatic Breast ◽  
Breast Cancer Patients

BackgroundLadiratuzumab vedotin (LV) is an investigational antibody-drug conjugate (ADC) composed of a humanized anti-LIV-1 IgG1 conjugated with monomethyl auristatin E (MMAE), a microtubule-disrupting agent. LV targets LIV-1, a protein expressed by various cancers. Along with a cytotoxic effect, LV has been shown to induce immunogenic cell death (ICD) in preclinical studies. LV is currently being investigated as a monotherapy and in combination with pembrolizumab in patients with metastatic breast cancer and other solid tumors. This correlative biomarker study aims to assess the ability of LV to modulate the tumor microenvironment (TME) in breast cancer patients.MethodsIn the SGNLVA-001 trial, metastatic breast cancer patients, predominantly of the triple negative subtype (TNBC), received LV monotherapy (2.0 or 2.5 mg/kg, every 3 weeks [q3w]). In the SGNLVA-002 trial, patients with metastatic TNBC received LV (2.0 or 2.5 mg/kg, q3w) plus pembrolizumab (200 mg, q3w). To investigate the potential effect of LV or LV plus pembrolizumab on the TME, paired pre-treatment and on-treatment tumor biopsies (Cycle [C] 1 Day [D] 5 or C1D15) were collected and analyzed by RNAseq and immunohistochemistry (IHC) staining.ResultsGene expression analysis of paired biopsy TNBC samples (n=59; baseline and C1D5) showed that LV monotherapy treatment significantly induces immune response-related gene expression, MHC, co-stimulatory molecules, and PD-L1. Gene set enrichment analysis (GSEA) demonstrated enrichment of macrophage and tumor inflammation signature genes, supporting the induction of ICD and enhancement of innate immune response. Paired tumor samples from subjects treated with LV plus pembrolizumab (n=16; baseline and C1D15) showed a broader range of gene expression changes on RNAseq compared to LV monotherapy. GSEA evidenced enrichment of genes associated with cytotoxic CD8 T cells, CD4 T helper cells, dendritic cells, and macrophages, further demonstrating the induction of ICD and activation of an innate immune response. Importantly, the combination had a unique adaptive immune response induction signature. IHC analysis confirmed the increased infiltration of macrophages after LV monotherapy. The combination with pembrolizumab resulted in a further increase in macrophages and a prominent influx of CD8 T cells.ConclusionsSystemic administration of LV monotherapy resulted in immune activation in the TME and macrophage infiltration. The combination of LV plus pembrolizumab resulted in a more potent immune activation in the TME and a prominent influx of CD8 T cells in addition to macrophages. Together these results provide a rationale for the continued clinical investigation of LV alone or in combination with pembrolizumab.Trial RegistrationNCT01969643 and NCT03310957Ethics ApprovalThe study protocols for clinical trials represented in this publication were reviewed by the respective IRB/IEC at each study site and approved before trial participants were screened and enrolled.ConsentNot applicable.

scholarly journals High KDM1A Expression Associated with Decreased CD8+T Cells Reduces the Breast Cancer Survival Rate in Patients with Breast Cancer

2021 ◽  
Vol 10 (5) ◽  
pp. 1112
Author(s):  
Hyung Suk Kim ◽  
Byoung Kwan Son ◽  
Mi Jung Kwon ◽  
Dong-Hoon Kim ◽  
Kyueng-Whan Min
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
T Cells ◽  
Survival Rate ◽  
Immune Responses ◽  
Cancer Patients ◽  
Cd8 T Cells ◽  
Specific Gene ◽  
Breast Cancer Patients ◽  
Gene Sets

Background: Lysine-specific demethylase 1A (KDM1A) plays an important role in epigenetic regulation in malignant tumors and promotes cancer invasion and metastasis by blocking the immune response and suppressing cancer surveillance activities. The aim of this study was to analyze survival, genetic interaction networks and anticancer immune responses in breast cancer patients with high KDM1A expression and to explore candidate target drugs. Methods: We investigated clinicopathologic parameters, specific gene sets, immunologic relevance, pathway-based networks and in vitro drug response according to KDM1A expression in 456 and 789 breast cancer patients from the Hanyang university Guri Hospital (HYGH) and The Cancer Genome Atlas, respectively. Results: High KDM1A expression was associated with a low survival rate in patients with breast cancer. In analyses of immunologic gene sets, high KDM1A expression correlated with low immune responses. In silico flow cytometry results revealed low abundances of CD8+T cells and high programmed death-ligand 1 (PD-L1) expression in those with high KDM1A expression. High KDM1A expression was associated with a decrease in the anticancer immune response in breast cancer. In pathway-based networks, KDM1A was linked directly to pathways related to the androgen receptor signaling pathway and indirectly to the immune pathway and cell cycle. We found that alisertib effectively inhibited breast cancer cell lines with high KDM1A expression. Conclusions: Strategies utilizing KDM1A may contribute to better clinical management/research for patients with breast cancer.

scholarly journals Oligoclonality of CD8+ T Cells in Breast Cancer Patients

1997 ◽  
Vol 3 (12) ◽  
pp. 836-851 ◽  
Author(s):  
Koichi Ito ◽  
James Fetten ◽  
Houman Khalili ◽  
Steven Hajdu ◽  
Erna Busch ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Cancer Patients ◽  
Cd8 T Cells ◽  
Breast Cancer Patients

scholarly journals GMFG Has Potential to Be a Novel Prognostic Marker and Related to Immune Infiltrates in Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Yan Yang ◽  
Xin He ◽  
Qian-Qian Tang ◽  
You-Cheng Shao ◽  
Wen-Jing Song ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Prognostic Marker ◽  
Cd8 T Cells ◽  
Cox Regression ◽  
Differentially Expressed Gene ◽  
Expression Level ◽  
Her2 Status ◽  
Breast Cancer Patients ◽  
Chemotherapy Drugs

A growing amount of evidence has indicated immune genes perform a crucial position in the development and progression of breast cancer microenvironment. The purpose of our study was to identify immunogenic prognostic marker and explore potential regulatory mechanisms for breast cancer. We identified the genes related to ImmuneScore using ESTIMATE algorithm and WGCNA analysis, and we identified the differentially expressed gene (DEGs). Then, Glia maturation factor γ (GMFG) was determined as a predictive factor by intersecting immune-related genes with DEGs and survival analysis. We found the expression of GMFG was lower in breast cancer tissues compared with normal breast tissues, which was further verified by immunohistochemical (IHC). Moreover, the decreased expression of GMFG was significantly related to the poor prognosis. Besides, the expression of GMFG was related to the age, ER status, PR status, HER2 status and tumor size, which further suggested that the expression of GMFG was correlated with the subtype and the growth of tumor. The univariate and multivariate Cox regression analyses revealed that age, stage, the expression level of GMFG and radiotherapy were independent factors for predicting the prognosis of breast cancer patients. Subsequently, a prognostic model to predict the 3-year, 5-year and 10-year overall survival rate was developed based on the above four variables, and visualized as a nomogram. The values of area under the curve of the nomogram at 3-year, 5-year and 10-year were 0.897, 0.873 and 0.922, respectively, which was higher than stage in prognostic accuracy. In addition, we also found that GMFG expression level was correlated with sensitivity of some breast cancer chemotherapy drugs. Furthermore, the results of GSEA indicated immune-related pathways were mainly enriched in GMFG-high-expression group. CIBERSORT analysis for the proportion of tumor-infiltrating immune cells (TIICs) suggested that expression of GMFG was positively association with multiple kinds T-cell in BC. Among them, CD8+ T cells had the strongest correlation with GMFG expression, which revealed that GMFG might has an antitumor effect by increasing the infiltration of CD8+ T cells in breast cancer. Accordingly, GMFG has the potential to become a novel immune biomarker for the diagnosis and treatment of breast cancer.

scholarly journals High WHSC1L1 Expression Reduces Survival Rates in Operated Breast Cancer Patients with Decreased CD8+ T Cells: Machine Learning Approach

2021 ◽  
Vol 11 (7) ◽  
pp. 636
Author(s):  
Hyung-Suk Kim ◽  
Kyueng-Whan Min ◽  
Dong-Hoon Kim ◽  
Byoung-Kwan Son ◽  
Mi-Jung Kwon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Cancer Patients ◽  
Cd8 T Cells ◽  
Survival Rates ◽  
Gradient Boosting ◽  
Breast Cancer Cell Lines ◽  
Breast Cancer Patients ◽  
Cancer Pathogenesis ◽  
Pathway Networks

Nuclear receptor-binding SET domain protein (NSD), a histone methyltransferase, is known to play an important role in cancer pathogenesis. The WHSC1L1 (Wolf-Hirschhorn syndrome candidate 1-like 1) gene, encoding NSD3, is highly expressed in breast cancer, but its role in the development of breast cancer is still unknown. The purpose of this study was to analyze the survival rates and immune responses of breast cancer patients with high WHSC1L1 expression and to validate the results using gradient boosting machine (GBM) in breast cancer. We investigated the clinicopathologic parameters, proportions of immune cells, pathway networks and in vitro drug responses according to WHSC1L1 expression in 456, 1500 and 776 breast cancer patients from the Hanyang University Guri Hospital, METABRIC and TCGA, respectively. High WHSC1L1 expression was associated with poor prognosis, decreased CD8+ T cells and high CD274 expression (encoding PD-L1). In the pathway networks, WHSC1L1 was indirectly linked to the regulation of the lymphocyte apoptotic process. The GBM model with WHSC1L1 showed improved prognostic performance compared with the model without WHSC1L1. We found that VX-11e, CZC24832, LY2109761, oxaliplatin and erlotinib were effective in inhibiting breast cancer cell lines with high WHSC1L1 expression. High WHSC1L1 expression could play potential roles in the progression of breast cancer and targeting WHSC1L1 could be a potential strategy for the treatment of breast cancer.

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