scholarly journals Differences in Tumor Immune Microenvironment in Metastatic Sites of Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Hyunjong Lee ◽  
Kwon Joong Na ◽  
Hongyoon Choi

Introduction: Tumor immune microenvironment (TIME) promotes immune escape, allowing for tumor progression and metastasis. In spite of the current evidence of the complicated role of immune cells in promoting or suppressing cancer progression, the heterogeneity of TIME according to the tumor site has been scarcely investigated. Here, we analyzed transcriptomic profiles of metastatic breast cancer to understand how TIME varies according to tumor sites.Methods: Two gene expression datasets from metastatic breast cancer of various sites and a single-cell RNA sequencing dataset of primary breast cancer and metastatic lymph nodes were analyzed. The immune cell-type enrichment of each tumor was estimated. Immune cell types were identified by clustering analysis, and the proportions of cell types in TIME were assessed according to the tumor site.Results: Metastatic bone lesions showed more neutrophils than breast lesions. Tumors clustered according to immune cell type were significantly associated with tumor site. In single-cell analyses, the TIMEs of metastatic lymph nodes showed fewer macrophages than those of primary tumors. Differentially expressed gene signatures in the primary tumor and metastatic lymph nodes were associated with macrophage activation.Conclusion: We conclude that metastatic sites show variable enrichment patterns of immune cells, and that the TIME of metastatic lesions should be considered in precise immuno-oncology treatments.

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5616
Author(s):  
Eugenia Fernandez ◽  
Luis Ubillos ◽  
Nabila Elgul ◽  
María Florencia Festari ◽  
Daniel Mazal ◽  
...  

Breast cancer is a public health concern and is currently the fifth cause of mortality worldwide. Identification of different biological subtypes is essential for clinical management; therefore, the role of pathologists is essential and useful tools for immunohistochemistry diagnosis are needed. Polypeptide-GalNAc-transferases are emerging novel biomarkers related to cancer behavior and GalNAc-T13, correlated with aggressiveness in some tumors, is an interesting candidate. Few monoclonal antibodies reacting with native proteins, and not affected by fixation and paraffin embedding, have been reported. The aim of this work was to develop a useful monoclonal antibody anti-GalNAc-T13 and to assess its potential significance in breast cancer diagnosis. We evaluated 6 human breast cancer cell lines, 338 primary breast tumors and 48 metastatic lymph nodes and looked for clinical significance correlating GalNAc-T13 expression with patients’ clinical features and survival. We found high GalNAc-T13 expression in 43.8% of the cases and observed a significant higher expression in metastatic lymph nodes, correlating with worse overall survival. We hypothesized several possible molecular mechanisms and their implications. We conclude that GalNAc-T13 may be a novel biomarker in breast cancer, useful for routine pathological diagnosis. Elucidation of molecular mechanisms related to aggressiveness should contribute to understand the role of GalNAc-T13 in breast cancer biology.


Oncotarget ◽  
2017 ◽  
Vol 8 (23) ◽  
pp. 37332-37341 ◽  
Author(s):  
Elise Furet ◽  
Morad El Bouchtaoui ◽  
Jean-Paul Feugeas ◽  
Catherine Miquel ◽  
Christophe Leboeuf ◽  
...  

2015 ◽  
Vol 30 (2) ◽  
pp. 174-183 ◽  
Author(s):  
Noriko Nemoto ◽  
Yukiko Shibahara ◽  
Hiroshi Tada ◽  
Keiko Uchida ◽  
Keely M. McNamara ◽  
...  

Background Neoadjuvant chemotherapy has been increasingly utilized in the treatment of breast cancer patients. However, there are no established surrogate markers predicting the response to subsequent adjuvant therapy and clinical outcome of patients. In particular, whether primary or lymph nodes metastasis should be evaluated for these analyses has remained unknown. Therefore, in this study, we first evaluated the differences in biomarkers between primary and metastatic cancer tissues in the patients undergoing neoadjuvant chemotherapy. We then correlated the findings with the clinical outcomes of these patients. Methods We examined 49 patients receiving neoadjuvant chemotherapy and subsequent surgery with lymph node metastasis. Estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2) and Ki-67 were all immunohistochemically evaluated in core needle biopsy samples from primary and metastatic tumors following chemotherapy. Results No statistically significant differences in these markers were detected between the primary tumor and metastatic lymph nodes following therapy, but the Ki-67 labeling index was significantly higher in metastatic lymph nodes than in primary tumor (p = 0.017). The patients associated with luminal A type carcinoma in their lymph nodes following chemotherapy demonstrated significantly better clinical outcomes (disease-free survival: p = 0.0045, overall survival: p = 0.0006) than those who were not. Conclusion These data indicate that subtype classification following chemotherapy, in the metastatic lymph nodes rather than primary tumor could predict long-term outcomes of patients undergoing neoadjuvant chemotherapy.


2012 ◽  
Vol 63 (1) ◽  
pp. 20-28 ◽  
Author(s):  
Yukiko Shibahara ◽  
Yasuhiro Miki ◽  
Takanori Ishida ◽  
Yasuhiro Nakamura ◽  
Takashi Suzuki ◽  
...  

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