Profiling of immune checkpoint biomarkers by multiplex immunofluorescence in breast cancer brain metastases.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2021-2021
Author(s):  
Gaia Griguolo ◽  
Anna Tosi ◽  
Valentina Guarneri ◽  
Maria Vittoria Dieci ◽  
Susan Fineberg ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Cell Density ◽  
Immune Checkpoint ◽  
Macrophage Polarization ◽  
M2 Macrophage ◽  
Marker Density ◽  
Immune Microenvironment ◽  
Significant Difference ◽  
M2 Macrophage Polarization

2021 Background: Despite potential clinical implications, the complexity of immune microenvironment in breast cancer (BC) brain metastases (BM) is still poorly understood. Multiplex immunofluorescence (mIF) allows simultaneous visualization of several IF labeled proteins while maintaining spatial information. This novel technique can be used to comprehensively describe BCBM immune microenvironment, potentially providing useful information to guide novel therapeutic approaches. Methods: Clinical data and archival BM samples from 60 BC patients undergoing neurosurgery (2003-2018) at three institutions were collected. BCBMs were characterized using a custom mIF panel, including immune checkpoint and co-inhibitory molecules (CD3, PD1, PD-L1, TIM3, LAG3, CD163) and localization (keratin for tumor recognition) markers. Mean marker density was determined by digital image analysis (positive cells/mm2) and classified in tumor and stroma areas. Associations between immune marker densities, BC subtype and overall survival from BM diagnosis (OS) were studied. Results: Sixty BCBM samples were analyzed; 32% HR+/HER2-, 38% HER2+, 30% HR-/HER2-. At a median follow-up of 43 months, the only clinical variable associated with OS was BC subtype (shortest for HR-/HER2- and longest for HER2+, p=0.02). In the total sample area and tumor area, no significant difference in marker density was observed according to BC subtype. In the stroma area, a significant difference in TIM3+ cell density was observed according to BC subtype (highest density in HR+/HER2- and lowest density in HER2+ tumors, Kruskal-Wallis p=0.017). Higher CD163 density (a marker of M2 macrophage polarization), both in the tumor and in the stroma area, was significantly associated with worse OS, even after correction by BC subtype. In the subgroup of patients with HR+/HER2- BCBM, high TIM3+ cell density in the stroma area was significantly associated with longer OS (median OS 54.1 versus 23 months respectively for TIM3+ density above and below median value; p=0.01). Conclusions: In BCBM, stromal TIM3+ immune infiltrate differs according to BC subtype. M2 macrophage polarization is consistently associated with worse OS across all BC subtypes and might represent a potential therapeutic target for these patients.[Table: see text]

scholarly journals Effects of Steady Low-Intensity Exercise on High-Fat Diet Stimulated Breast Cancer Progression Via the Alteration of Macrophage Polarization

2020 ◽  
Vol 19 ◽  
pp. 153473542094967
Author(s):  
Min Kyoon Kim ◽  
Yesl Kim ◽  
SeungHwa Park ◽  
Eunju Kim ◽  
Yerin Kim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
High Fat Diet ◽  
Tumor Volume ◽  
Macrophage Polarization ◽  
M2 Macrophage ◽  
High Fat ◽  
Low Intensity ◽  
M2 Macrophage Polarization ◽  
Low Intensity Exercise

Physical inactivity and high-fat diet, especially high saturated fat containing diet are established risk factors for breast cancer that are amenable to intervention. High-fat diet has been shown to induce tumor growth and metastasis by alteration of inflammation but steady exercise has anti-tumorigenic effects. However, the mechanisms underlying the effects of physical activity on high-fat diet stimulated breast cancer initiation and progression are currently unclear. In this study, we examined how the intensity of physical activity influences high fat diet-stimulated breast cancer latency and progression outcomes, and the possible mechanisms behind these effects. Five-week-old female Balb/c mice were fed either a control diet or a high-fat diet for 8 weeks, and then 4T1 mouse mammary tumor cells were inoculated into the mammary fat pads. Exercise training occurred before tumor cell injection, and tumor latency and tumor volume were measured. Mice with a high-fat diet and low-intensity exercise (HFLE) had a longer tumor latency period, slower tumor growth, and smaller tumor volume in the final tumor assessment compared with the control, high-fat diet control (HFDC), and high-fat diet with moderate-intensity exercise (HFME) groups. Steady low- and moderate-intensity exercise had no effect on cell proliferation but induced apoptosis by activating caspase-3 through the alteration of Bcl-2, Bcl-xL, and Bax expression. Furthermore, steady exercise reduced M2 macrophage polarization in breast tumor tissue, which has been linked to tumor growth. The myokine, myostatin, reduced M2 macrophage polarization through the inhibition of the JAK-STAT signaling pathway. These results suggest that steady low-intensity exercise could delay breast cancer initiation and growth and reduce tumor volume through the induction of tumor cell apoptosis and the suppression of M2 macrophage polarization.

Immune microenvironment profiling of breast cancer brain metastases using multiplex immunofluorescence.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 2526-2526
Author(s):  
Gaia Griguolo ◽  
Anna Tosi ◽  
Valentina Guarneri ◽  
Maria Vittoria Dieci ◽  
Susan Fineberg ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Spatial Information ◽  
Immune Cell ◽  
Total Sample ◽  
Clinical Variable ◽  
Immune Microenvironment ◽  
Significant Difference ◽  
Tumor Recognition ◽  
Breast Cancer Brain Metastases

2526 Background: Despite clinical implications, the complexity of brain metastases (BM) immune microenvironment in breast cancer (BC) patients is poorly understood. Multiplex immunofluorescence (mIF), a novel imaging technique allowing simultaneous visualization and quantification of several IF labeled proteins while maintaining spatial information, holds promise to comprehensively describe BCBM immune microenvironment, potentially providing valuable information to improve treatment. Methods: Clinical data and archival BM samples were collected for 60 BC patients undergoing neurosurgery (2003-2018) at three institutions. BM immune contexture was characterized using a custom mIF panel, including cell subtyping (CD4, CD8, FOXP3, CD68), activation (Granzyme B) and localization (keratin for tumor recognition) markers. Mean immune cell density (cells/mm2) for each sample was determined by digital image analysis and classified in tumor and stroma areas. Associations between immune subpopulations, BC subtype and overall survival from BM diagnosis (OS) were studied. Results: Up to date, 30 BCBM samples have been analyzed; 33% HR+/HER2-, 20% HR-/HER2+, 10% HR+/HER2+, 37% HR-/HER2-. At a median follow-up of 46 months, BC subtype was the only clinical variable associated with OS (longest for HER2+ and shortest for HR-/HER2-, log-rank p = 0.002). In the total sample area, no significant difference in immune cell densities was observed according to BC subtype. In the tumor area, HR+/HER2- tumors showed higher densities of CD8+ and CD68+ cells compared to other subtypes (p = 0.036 and p = 0.016, respectively). In stroma, HR-/HER2- tumors presented numerically higher densities of CD4+ and FOXP3+ cells and higher ratio of CD4/CD8 and FOXP3/CD8 ratio (not statistically significant). Higher CD4/CD8 and FOXP3/CD8 ratio in the stroma was significantly associated with worse OS, even after correction by BC subtype (Table). Conclusions: In BCBM, immune infiltrate differs according to BC subtype. Preliminary results suggest that a more tolerogenic immune microenvironment is associated with worse OS and might represent a target for optimization of immunotherapy for these patients. Updated results for all 60 patients will be presented. [Table: see text]

scholarly journals LncRNA GNAS-AS1 facilitates ER+ breast cancer cells progression by promoting M2 macrophage polarization via regulating miR-433-3p/GATA3 axis

2020 ◽  
Vol 40 (7) ◽  
Author(s):  
Shi-Qin Liu ◽  
Zhi-Yang Zhou ◽  
Xue Dong ◽  
Lei Guo ◽  
Ke-Jing Zhang
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Macrophage Polarization ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
M2 Macrophage ◽  
Physical And Mental Health ◽  
Reporter System ◽  
M2 Macrophage Polarization

Abstract Objective: ER+ breast cancer is the most common type of breast cancer, which seriously affects the physical and mental health of women. Recently, lncRNAs mediated tumor-associated macrophages (TAM) were identified to involve in tumorigenesis. Therefore, the present study aimed at demonstrating the regulatory network of GNAS-AS1 in TAM-mediated ER+ breast cancer progress. Methods: The expression levels of genes were evaluated using qRT-PCR. The proportions of polarized macrophages (M1, M2) were assessed by flow cytometry. Cell proliferation, migration and invasion were evaluated by CCK-8, wound healing and transwell assay, respectively. Double-luciferase reporter system was used to detect the interaction between molecules. Western blot was applied to test protein levels. Results: The expression of GNAS-AS1 was obviously increased in ER+ breast cancer tissues and cell lines, as well as M2 macrophages. GNAS-AS1 facilitated the capabilities of proliferation, migration and invasion of ER+ breast cancer cells by accelerating M2 macrophage polarization via directly sponging miR-433-3p. GATA3, as a target of miR-433-3p, could positively regulate by GNAS-AS1. Furthermore, either miR-433-3p overexpression or GATA3 knockdown impaired the effects of GNAS-AS1 on M2 macrophage polarization and ER+ breast cancer cells progression. Conclusion: GNAS-AS1/miR-433-3p/GATA3 axis promoted proliferation, metastasis of ER+ breast cancer cells by accelerating M2 macrophage polarization. The mechanism may provide a new strategy and target for ER+ breast cancer treatment.

scholarly journals M2 macrophage polarization in chronic spontaneous urticaria refractory to antihistamine treatment

2021 ◽  
Author(s):  
Roberta F.J. Criado ◽  
Paulo Ricardo Criado ◽  
Carla Pagliari ◽  
Mirian N. Sotto ◽  
Carlos D'Apparecida Machado Filho ◽  
...  
Keyword(s):  
Macrophage Polarization ◽  
Chronic Spontaneous Urticaria ◽  
M2 Macrophage ◽  
M2 Macrophage Polarization
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