Immunobiology of tumour-adjacent breast tissue
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Date
2020-02-13
Authors
Paiva, Alen
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Abstract
Tumour-reactive immune cells are crucial for tumour rejection and for development of immunotherapies against breast cancer tumours. Paradoxically tumour infiltrating leukocytes (TILs) in the tumour microenvironment have been shown to augment tumour cell proliferation, contrasting to their normal physiological role which is to detect and eliminate malignant cells. In silico studies have revealed the presence of inflammatory response in tumour-adjacent tissue. However, the ability of immune cells from tumour-adjacent tissue to detect and eliminate breast cancer cells has not been studied nor functionally validated before. The research in this thesis investigated the immune cell composition of the normal breast tissue, tumour and matched tumour-adjacent breast tissue with immune cell phenotyping array panel. The immune cell phenotyping revealed the presence of a higher number of T regulatory cells in tumour tissue and a significantly lower number of T regulatory cells in tumour-adjacent tissue. To examine the anti-tumour activities of the immune cells present in the tumour-adjacent breast tissue a new 3 dimensional Matrigel co-culture system was developed and optimized. Using this 3D co-culture system I observed that the immune cells from tumour-adjacent tissue significantly reduced the breast cancer cell number in the co-culture experiments demonstrating their ability to detect and eliminate matched breast cancer cells without immune cell activation. However, the same immune cells showed no reactivity towards the healthy breast cells obtained from the tumour-adjacent tissue. The research done in this thesis provides valuable information that can be used as the basis for the development of immunotherapies against breast cancer tumours to prevent tumour metastasis and enhance disease-free survival.
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Keywords
Immunology, Breast cancer, Tumour-adjacent tissue