Abstract P5-04-05: Co-stimulation through 4-1BB/CD137 improves expansion and function of tumor-infiltrating T lymphocytes from primary and metastatic triple-negative breast cancer and inflammatory breast cancer

2015 ◽  
Author(s):  
Michiko Harao ◽  
Hui Gao ◽  
Jie Qing Chen ◽  
Elizabeth A Mittendorf ◽  
Gildy V Babiera ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Lymphocytes ◽  
Inflammatory Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
And Function

scholarly journals FGFR3 signaling and function in triple negative breast cancer

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Nicole J. Chew ◽  
Elizabeth V. Nguyen ◽  
Shih-Ping Su ◽  
Karel Novy ◽  
Howard C. Chan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
And Function

scholarly journals Infiltration of CD8+ T cells into tumor cell clusters in triple-negative breast cancer

2019 ◽  
Vol 116 (9) ◽  
pp. 3678-3687 ◽  
Author(s):  
Xuefei Li ◽  
Tina Gruosso ◽  
Dongmei Zuo ◽  
Atilla Omeroglu ◽  
Sarkis Meterissian ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Tumor Cell ◽  
Cell Density ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Spatial Profile ◽  
Cell Clusters

Infiltration of CD8+ T lymphocytes into solid tumors is associated with good prognosis in various types of cancer, including triple-negative breast cancer (TNBC). However, the mechanisms underlying different infiltration levels are largely unknown. Here, we have characterized the spatial profile of CD8+ T cells around tumor cell clusters (tightly connected tumor cells) in the core and margin regions in TNBC patient samples. We found that in some patients, the CD8+ T cell density first decreases when moving in from the boundary of the tumor cell clusters and then rises again when approaching the center. To explain various infiltration profiles, we modeled the dynamics of T cell density via partial differential equations. We spatially modulated the diffusion/chemotactic coefficients of T cells (to mimic physical barriers) or introduced the localized secretion of a diffusing T cell chemorepellent. Combining the spatial-profile analysis and the modeling led to support for the second idea; i.e., there exists a possible chemorepellent inside tumor cell clusters, which prevents CD8+ T cells from infiltrating into tumor cell clusters. This conclusion was consistent with an investigation into the properties of collagen fibers which suggested that variations in desmoplastic elements does not limit infiltration of CD8+ T lymphocytes, as we did not observe significant correlations between the level of T cell infiltration and fiber properties. Our work provides evidence that CD8+ T cells can cross typical fibrotic barriers and thus their infiltration into tumor clusters is governed by other mechanisms possibly involving a local repellent.

Aspirin attenuates YAP and β-catenin expression by promoting β-TrCP to overcome docetaxel and vinorelbine resistance in triple-negative breast cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13099-e13099
Author(s):  
Ji Ma ◽  
Hongwei Xia ◽  
Zhenhai Fan ◽  
Qiulin Tang ◽  
Tao Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Predictive Biomarker ◽  
Drug Resistant ◽  
Combined Use ◽  
And Function

e13099 Background: YAP and β-catenin play critical roles in the carcinogenesis of several cancers, but their functions in chemoresistance remain unclear in triple-negative breast cancer (TNBC). Herein, we examined the expression and function of the two proteins in the chemoresistance of TNBC. Methods: We examined the expression levels of YAP and β-catenin in TNBC samples by immunohistochemistry (IHC) and their roles in prognosis. Dynamic changes in the two proteins in TNBC tissues were determined by RT-PCR. CCK-8 assays, colony formation assays, flow cytometry, migration assays and nude mouse models were used to investigate the functions of YAP and β-catenin in drug-resistant TNBC cells. The involved signalling pathways were detected by western blot assays. Results: TNBC patients with high YAP and/or β-catenin expression had a higher risk of relapse or mortality than patients with low YAP and/or β-catenin expression, and changes in the expression of the two proteins might be a promising predictive biomarker for neoadjuvant chemotherapy sensitivity. Inhibition of YAP or β-catenin enhanced the cytotoxicity of the anti-microtubule agents docetaxel and vinorelbine against TNBC cells in vitro and in vivo. Moreover, YAP and β-catenin were upregulated in docetaxel- or vinorelbine-resistant TNBC cells, while inhibition of YAP or β-catenin enhanced the sensitivity of drug-resistant cells. Interestingly, aspirin, a kind of acetylsalicylic acid, reversed the drug resistance of cells and in combination with aspirin and docetaxel or vinorelbine significantly inhibited the growth of drug-resistant TNBC cells. The involved mechanism is that aspirin impaired YAP or β-catenin expression by upregulating the E3 ubiquitin ligase β-TrCP. Conclusions: Both YAP and β-catenin act as key biomarkers of prognosis and anti-microtubule drug resistance in TNBC, and the combined use of aspirin and anti-microtubule drugs inhibits YAP and β-catenin, presenting several promising therapeutic approaches for TNBC treatment.

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