Abstract P3-01-13: Co-expression of molecules associated with innate and adaptive immune response on single CTCs of patients with metastatic breast cancer (mBC)

2019 ◽  
Author(s):  
D Mavroudis ◽  
MA Papadaki ◽  
PG Tsoulfas ◽  
K Troullinou ◽  
CA Apostolopoulou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
Metastatic Breast Cancer ◽  
Adaptive Immune Response ◽  
Metastatic Breast ◽  
Adaptive Immune ◽  
Single Ctcs

scholarly journals Effect of yoga on sleep quality and neuroendocrine immune response in metastatic breast cancer patients

2017 ◽  
Vol 23 (3) ◽  
pp. 253 ◽  
Author(s):  
RaghavendraMohan Rao ◽  
HS Vadiraja ◽  
R Nagaratna ◽  
KS Gopinath ◽  
Shekhar Patil ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
Metastatic Breast Cancer ◽  
Sleep Quality ◽  
Cancer Patients ◽  
Metastatic Breast ◽  
Breast Cancer Patients

scholarly journals Cancer cell CCR2 orchestrates suppression of the adaptive immune response

2020 ◽  
Vol 217 (10) ◽  
Author(s):  
Miriam R. Fein ◽  
Xue-Yan He ◽  
Ana S. Almeida ◽  
Emilis Bružas ◽  
Arnaud Pommier ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cells ◽  
Adaptive Immune Response ◽  
Adaptive Immune ◽  
Genetic Targeting ◽  
Dc Maturation

C-C chemokine receptor type 2 (CCR2) is expressed on monocytes and facilitates their recruitment to tumors. Though breast cancer cells also express CCR2, its functions in these cells are unclear. We found that Ccr2 deletion in cancer cells led to reduced tumor growth and approximately twofold longer survival in an orthotopic, isograft breast cancer mouse model. Deletion of Ccr2 in cancer cells resulted in multiple alterations associated with better immune control: increased infiltration and activation of cytotoxic T lymphocytes (CTLs) and CD103+ cross-presenting dendritic cells (DCs), as well as up-regulation of MHC class I and down-regulation of checkpoint regulator PD-L1 on the cancer cells. Pharmacological or genetic targeting of CCR2 increased cancer cell sensitivity to CTLs and enabled the cancer cells to induce DC maturation toward the CD103+ subtype. Consistently, Ccr2−/− cancer cells did not induce immune suppression in Batf3−/− mice lacking CD103+ DCs. Our results establish that CCR2 signaling in cancer cells can orchestrate suppression of the immune response.

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.

Urinary Neopterin, Serum Retinol, α-tocopherol and Homocysteine in Breast Cancer Patients During Treatment with Bevacizumab and Chemotherapy

Pteridines ◽  
2010 ◽  
Vol 21 (1) ◽  
pp. 87-93 ◽  
Author(s):  
Bohuslav Melichar ◽  
Hana Kalábová ◽  
Lenka Krčmová ◽  
Markéta Kašparová ◽  
Jiří Plíšek ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
External Beam Radiation ◽  
C Reactive Protein ◽  
Systemic Immune Response ◽  
Beam Radiation ◽  
Reactive Protein ◽  
Urinary Neopterin

Abstract Bevacizumab, monoclonal antibody targeting vascular endothelial growth factor, is effective in different tumors, including colorectal carcinoma, non-small cell lung cancer, renal cell carcinoma and breast cancer. Increased serum or urinary concentrations of neopterin, an indicator of systemic immune response, have been described in patients with tumors of different primary locations, and further increase has been observed during anticancer therapy. An increase of urinary neopterin has been described after administration of cytokines, cytotoxic chemotherapy, or external beam radiation, but less is known about the effects of targeted agents on systemic immune response. We have studied serum homocysteine, C-reactive protein, α-tocopherol and retinol, and urinary neopterin in patients with metastatic breast cancer treated with bevacizumab, taxane and carboplatin. Homocysteine and C-reactive protein were determined immunochemically. α-tocopherol, retinol and urinary neopterin were determined by high performance liquid chromatography. Homocysteine, C-reactive protein and urinary neopterin decreased, while retinol and α-tocopherol increased during the therapy. In conclusion, the treatment of patients with metastatic breast cancer with bevacizumab, taxane and carboplatin resulted in the suppression of systemic inflammatory and immune response. The suppression of systemic inflammatory and immune response was associated with an increase in serum vitamin concentrations.

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