Immunological Changes during Tumour Growth in Triple-Negative Breast Cancer

Abstract

Breast cancer ranks as the second most prevalent cancer globally and is the leading cause of cancer-related deaths among women. Breast cancer is a heterogeneous group and can be divided into several subtypes with different prognoses and treatment regimens. One of the subtypes of breast cancer, known as triple-negative breast cancer (TNBC), accounts for about 10% of breast cancer cases and is known for its poor prognosis and limited treatment options. The immune system's role in breast cancer is intricate, initially fighting the tumour but often shifting to support its growth as the cancer progresses. Tumour size is one of the most important prognostic factors in breast cancer, with larger tumour size associated with more advanced disease and a greater chance of metastasis. Despite this knowledge, the biological processes behind tumour growth and the role of the immune system in this process are still not well understood.

The overall aim of this thesis was to investigate the immunological changes during tumour growth in TNBC.

RNA-sequencing was conducted on 40 primary triple-negative breast tumours, followed by deconvolution to determine the relative percentages of 22 distinct immune cell types. Immune infiltration and immune cell populations were compared between small and large tumours to explore changes that occur during tumour growth. The deconvolution results were also evaluated alongside other immune cell detection methods. Additionally, a clustering analysis was conducted to determine the influence of various clinical features on the immune cell populations. An analysis of differentially expressed genes was also carried out to identify transcriptomic alterations linked to the immune system as the tumours developed.

The analysis indicated no significant differences in immune cell populations between small and large TNBC tumours, but the degree of immune infiltration, regardless of tumour size, showed clear differences in immune cell composition. Tumours with low immune infiltration were dominated by macrophages, while a greater variety of immune cell types were present in tumours with high immune infiltration. The study also found that genes related to the immune system and cell communication were downregulated in larger tumours. This suggests that the tumour changes as it grows. Although the number of immune cells remains the same, the immune response becomes less effective as the tumour progresses.