1. The Role of TIPE2 Protein in Invasive Breast Carcinoma
By Frances Maher
University of Pennsylvania
Coordinating Center: Stanford University

2. Outline Introduction Central Hypothesis Specific Studies Conclusions
Invasive Breast Carcinoma
Invasive Breast Carcinoma and the Immune System
TIPE2
Central Hypothesis
Specific Studies
Conclusions

3. Invasive Breast Carcinoma
Results from uncontrolled cell growth in the lobule (milk-producing glands) and lactiferous duct (channels that transport milk)
Second leading cause of cancer death among women and 1 in 8 US women will be diagnosed with invasive breast cancer
The need for improved therapeutic approaches is urgent and crucial
American Cancer Society, 2016
U.S. National Library of Medicine, 2015

4. Invasive Breast Carcinoma and the Immune System
Acute inflammatory response
TH-1 Leukocyte
Tumor Cytotoxicity- Toxic to tumor cells
Tumor destruction
Macrophage Polarization- When a macrophage activates different functions based on the molecular environment
Leukocytes- White blood cell that defends foreign molecules and disease
Macrophage- White blood cell that digests cellular/foreign wastes
DeNardo. et al. Breast Cancer Research (2007) 9:212

5. Tumor Rejection

6. Invasive Breast Carcinoma and the Immune System
Chronic inflammatory response
TH-2 Leukocyte and T Regulatory Cell (Leukocyte)
Angiogenesis- Production of new blood vessels
Secretes anti-inflammatory factors
Promotes Tumor Microenvironment
Anti-Inflammatory Factors- Substance that turns off immune response
Leukocytes- White blood cell that defends foreign molecules and disease
DeNardo. et al. Breast Cancer Research (2007) 9:212

7. Tumor Promotion

8. TIPE2 Tumor necrosis factor-α-induced protein like-2
Regulator of inflammation and immune homeostasis
Inhibitor in lung and colon cancer
________ in breast cancer
Honghong, S. et al. Cell. (2008) 133(3):

9. MAIN HYPOTHESIS
TIPE2 is involved in invasive breast carcinoma progression by regulating the immune response

10. Study 1:
Determine the survival rates among breast cancer patients with varying TIPE2 mRNA expression

11. Invasive Breast Carcinoma Survival Rates
Patients with HIGH TIPE2
Patients with LOW TIPE2
(Sample Size: 1105 patients)
Oncolnc Analysis
TCGA, Cell 2012

12. Study 2:
Determine the expression levels of TIPE2 mRNA in different types of cancer cell lines

13. TIPE2 mRNA Cancer Cell Line Analysis
Immune-related cancers
Non-immune related cancers
CCLE Analysis

14. Study 3:
Determine the pathway that TIPE2 is involved in during breast cancer progression

15. Genes Coexpressed with TIPE2 in Invasive Breast Carcinoma
Pearson’s Correlation- Linear correlation between two variables
CD-4
TIPE2
Brady, RL. Science. (1993) 260 (5110): 979–83.
TCGA, Cell 2015

16. Pathways of Genes Coexpressed with TIPE2 in Breast Cancer
Gene Set Enrichment Analysis- Aims to find genes correlated with disease phenotypes by pinpointing specific genes that are overrepresented in a group of genes.
Immune-related pathways/processes
ClueGO Analysis

17. Conclusions
Upregulation of TIPE2 mRNA is correlated with favorable patient prognosis in breast cancer
TIPE2 gene expression is associated with immune functions in breast cancer
TIPE2 may serve as a novel prognostic biomarker and therapeutic target for invasive breast cancer

18. Correlated with Immune Cell Functions and Migration in Breast Cancer
Increased TIPE2 mRNA
Correlated with Immune Cell Functions and Migration in Breast Cancer
Higher Survival

19. Thank You for your time!

20. Acknowledgements University of Pennsylvania Stanford University
Dr.Halpern-Felsher
Dr.Li
Ms.McLaughlin
Dr.Chen
Dr.Cathopoulis
National Institutes of Health STEP-UP
Dr.Rivers