scholarly journals CCL5 promotes breast cancer recurrence through macrophage recruitment in residual tumors

2019 ◽  
Author(s):  
Andrea Walens ◽  
Ashley V. DiMarco ◽  
Ryan Lupo ◽  
Benjamin R. Kroger ◽  
Jeffrey S. Damrauer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Cells ◽  
Tumor Recurrence ◽  
Immune Cell ◽  
Cancer Recurrence ◽  
Residual Tumor ◽  
Breast Cancer Recurrence ◽  
Immune Cell Infiltration ◽  
Conditional Mouse Model

ABSTRACTOver half of breast cancer related deaths are due to recurrence five or more years after initial diagnosis and treatment. This latency suggests that a population of residual tumor cells can survive treatment and persist in a dormant state for many years. The role of the microenvironment in regulating the survival and proliferation of residual cells following therapy remains unexplored. Using a conditional mouse model for Her2-driven breast cancer, we identify interactions between residual tumor cells and their microenvironment as critical for promoting tumor recurrence. Her2 downregulation leads to an inflammatory program driven by TNFα/NFκB signaling, which promotes immune cell infiltration in regressing and residual tumors. The cytokine CCL5 is elevated following Her2 downregulation and remains high in residual tumors. CCL5 promotes tumor recurrence by recruiting CCR5-expressing macrophages, which may contribute to collagen deposition in residual tumors. Blocking this TNFα-CCL5-macrophage axis may be efficacious in preventing breast cancer recurrence.

scholarly journals CCL5 promotes breast cancer recurrence through macrophage recruitment in residual tumors

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Andrea Walens ◽  
Ashley V DiMarco ◽  
Ryan Lupo ◽  
Benjamin R Kroger ◽  
Jeffrey S Damrauer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Cells ◽  
Tumor Recurrence ◽  
Immune Cell ◽  
Cancer Recurrence ◽  
Residual Tumor ◽  
Breast Cancer Recurrence ◽  
Immune Cell Infiltration ◽  
Conditional Mouse Model

Over half of breast-cancer-related deaths are due to recurrence 5 or more years after initial diagnosis and treatment. This latency suggests that a population of residual tumor cells can survive treatment and persist in a dormant state for many years. The role of the microenvironment in regulating the survival and proliferation of residual cells following therapy remains unexplored. Using a conditional mouse model for Her2-driven breast cancer, we identify interactions between residual tumor cells and their microenvironment as critical for promoting tumor recurrence. Her2 downregulation leads to an inflammatory program driven by TNFα/NFκB signaling, which promotes immune cell infiltration in regressing and residual tumors. The cytokine CCL5 is elevated following Her2 downregulation and remains high in residual tumors. CCL5 promotes tumor recurrence by recruiting CCR5-expressing macrophages, which may contribute to collagen deposition in residual tumors. Blocking this TNFα-CCL5-macrophage axis may be efficacious in preventing breast cancer recurrence.

scholarly journals RIPK3 upregulation confers robust proliferation and collateral cystine-dependence on breast cancer recurrence

2019 ◽  
Author(s):  
Chao-Chieh Lin ◽  
Nathaniel Mabe ◽  
Yi-Tzu Lin ◽  
Wen-Hsuan Yang ◽  
Xiaohu Tang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Cells ◽  
Breast Tumor ◽  
Tumor Recurrence ◽  
Cancer Recurrence ◽  
Breast Cancer Recurrence ◽  
Recurrent Tumor ◽  
Breast Tumor Cells ◽  
Recurrent Tumors ◽  
Recurrent Breast

AbstractThe molecular and genetic basis of tumor recurrence is complex and poorly understood. RIPK3 is a key effector in programmed necrotic cell death and, therefore, its expression is frequently suppressed in primary tumors. In a transcriptome profiling between primary and recurrent breast tumor cells from a murine model of breast cancer recurrence, we found that RIPK3, while absent in primary tumor cells, is dramatically re-expressed in recurrent breast tumor cells by an epigenetic mechanism. Unexpectedly, we found that RIPK3 knockdown in recurrent tumor cells reduced clonogenic growth, causing cytokinesis failure, p53 stabilization, and repressed the activities of YAP/TAZ. These data uncover a surprising role of the pro-necroptotic RIPK3 kinase in enabling productive cell cycle during tumor recurrence. Remarkably, high RIPK3 expression also rendered recurrent tumor cells exquisitely dependent on extracellular cystine and undergo programmed necrosis upon cystine deprivation. The induction of RIPK3 in recurrent tumors unravels an unexpected mechanism that paradoxically confers on tumors both growth advantage and necrotic vulnerability, providing potential strategies to eradicate recurrent tumors.

scholarly journals Role of tumor cells contaminating the graft in breast cancer recurrence after high-dose chemotherapy

1997 ◽  
Vol 20 (2) ◽  
pp. 167-169 ◽  
Author(s):  
P Pedrazzoli ◽  
M Battaglia ◽  
GADa Prada ◽  
A Lanza ◽  
A Cuomo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Cells ◽  
Cancer Recurrence ◽  
High Dose Chemotherapy ◽  
Breast Cancer Recurrence ◽  
High Dose

The role of FDG PET/CT in patients with locoregional breast cancer recurrence: A comparison to conventional imaging techniques

2010 ◽  
Vol 36 (4) ◽  
pp. 387-392 ◽  
Author(s):  
T.S. Aukema ◽  
E.J.Th. Rutgers ◽  
W.V. Vogel ◽  
H.J. Teertstra ◽  
H.S. Oldenburg ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Fdg Pet ◽  
Imaging Techniques ◽  
Cancer Recurrence ◽  
Breast Cancer Recurrence ◽  
Conventional Imaging ◽  
Pet Ct ◽  
Fdg Pet Ct

scholarly journals The Role of Metastasectomy in Women with Solitary Metastatic Breast Cancer Recurrence

2018 ◽  
Vol 1 (1) ◽  
Author(s):  
Patrick Mun Yew Chan ◽  
Sherwin Kuah ◽  
Mui Heng Goh ◽  
Sarah Qinghui Lu ◽  
Juliana Jia Chuan Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Recurrence ◽  
Metastatic Breast ◽  
Breast Cancer Recurrence

scholarly journals Prognostic Influence of Residual Tumor-Infiltrating Lymphocyte Subtype After Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Jesse Lopes da Silva ◽  
Lucas Zanetti de Albuquerque ◽  
Fabiana Resende Rodrigues ◽  
Guilherme Gomes de Mesquita ◽  
Priscila Valverde Fernandes ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Immune Cell ◽  
Clinical Stage ◽  
Residual Tumor ◽  
Tissue Microarrays ◽  
Curative Surgery

ObjectiveThis study aimed to examine the prevalence and prognostic role of tumor microenvironment (TME) in triple-negative breast cancer (TNBC) after neoadjuvant chemotherapy (NACT) through immunohistochemical characterization.MethodsThe internal database of the Brazilian National Cancer Institute for women diagnosed with TNBC who underwent NACT and thereafter curative surgery between January 2010 and December 2014 was queried out. Core biopsy specimens and tissue microarrays containing surgical samples of TNBC from 171 and 134 women, respectively, were assessed by immunohistochemistry for CD3, CD4, CD8, CD14, CD56, CD68, CD117, FOXP3, PD-1, PD-L1, and PD-L2. Immune cell profiles were analyzed and correlated with response and survival.ResultsMean age was 50.5 years, and most cases were clinical stage III [143 cases (83.6%)]. According to the multivariate analysis, only Ki67 and clinical stage significantly influenced the pattern of response to systemic treatment (p = 0.019 and p = 0.033, respectively). None of the pre-NACT IHC markers showed a significant association with event-free survival (EFS) or overall survival (OS). As for post-NACT markers, patients with high CD14 had significantly shorter EFS (p = 0.015), while patients with high CD3 (p = 0.025), CD4 (p = 0.025), CD8 (p = 0.030), CD14 (p = 0.015), FOXP3 (p = 0.005), high CD4/FOXP3 (p = 0.034), and CD8/FOXP3 (p = 0.008) showed longer EFS. Only high post-NACT CD4 showed significantly influenced OS (p = 0.038).ConclusionThe present study demonstrated that the post-NACT TIL subtype can be a determining factor in the prognosis of patients with TNBC.

Abstract 1419: Role of p70S6K in breast cancer recurrence

2011 ◽  
Author(s):  
Barbara Belletti ◽  
Maura Sonego ◽  
Stefania Berton ◽  
Tiziana Perin ◽  
Samuele Massarut ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Recurrence ◽  
Breast Cancer Recurrence
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