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The contribution of macrophages to tumour growth and metastasis

Bart, Valentina 2021. The contribution of macrophages to tumour growth and metastasis. PhD Thesis, Cardiff University.
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Abstract

Triple negative breast cancer (TNBC) accounts for 10 to 20 percent of breast cancers diagnosed and with a poor response to therapeutic options is associated with high mortality. The immune cell infiltrate of breast cancers is dominated by tumour associated macrophages (TAMs), which have the potential to eliminate tumour cells, but have also been implicated in various processes supporting tumour growth. For the work summarisedin this thesis, it was hypothesised that different types of TAMs exist in TNBC that could differently affect tumour outcome. Single cell sequencing of immune cells in the 4T1 mouse model of breast cancer allowed the identification of four different TAM subsets, some of which have not been described before. The work summarised in this thesis indicates that a global reduction of all TAM populations is not beneficial in reducing primary tumour growth, but does reduce metastatic burden in the lungs. While the effects of TAMs and regulatory T cells (Tregs) on each other could not be deciphered, the data do suggest that acombination of immune-targeting therapeutics affecting these two cell populations needs careful consideration, as a combined inhibition of both TAMs and Tregs resulted in the loss of all effects observed with either therapeutic on its own.

Item Type: Thesis (PhD)
Date Type: Completion
Status: Unpublished
Schools: Medicine
Date of First Compliant Deposit: 8 February 2022
Last Modified: 19 Apr 2023 08:28
URI: https://orca.cardiff.ac.uk/id/eprint/147306

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