The relationship of the immune system and tumour cells is complex; although recognised that the immune system can protect the host against tumour development, the immune system also facilitates tumour progression thro...The relationship of the immune system and tumour cells is complex; although recognised that the immune system can protect the host against tumour development, the immune system also facilitates tumour progression through immune suppression. Pro-inflammatory mediators associated with chronic inflammation are responsible for the expansion and activation of myeloid derived suppressor cells(MDSCs); a heterogeneous group of cells that originates from myeloid progenitor cells but does not complete the final stages of differentiation. A causal relationship between chronic inflammation and tumour progression relies on the accumulation and maintenance of MDSCs as its linchpin; responsible for immunosuppression through the down-regulation of antitumour responses. MDSCs cause immunosuppression through a number of mechanisms; inhibiting the proliferation of CD4^+ and CD8^+ T cells, blocking natural killer cell activation and limiting dendritic cell maturation and function. As well as using various mechanisms to inhibit adaptive and immune responses, MDSCs also have non-immunological functions that aid tumour spread; including directly promoting tumour proliferation and metastasis by having an important role in tumour angiogenesis, secretion of matrix metalloproteinases and induction of epithelial-mesenchymal transition. Breast cancer is the most common cancer among women in the United Kingdom with 44540 new cases of invasive carcinoma in 2013 and results in the second highest cancer mortality rate in women, with 11600 deaths in 2012. Considering this, the need for novel therapeutic interventions is higher than ever. This review summarises the rationale for the targeting of MDSCs in breast cancer as a realistic avenue to increase survival from breast cancer.展开更多
文摘The relationship of the immune system and tumour cells is complex; although recognised that the immune system can protect the host against tumour development, the immune system also facilitates tumour progression through immune suppression. Pro-inflammatory mediators associated with chronic inflammation are responsible for the expansion and activation of myeloid derived suppressor cells(MDSCs); a heterogeneous group of cells that originates from myeloid progenitor cells but does not complete the final stages of differentiation. A causal relationship between chronic inflammation and tumour progression relies on the accumulation and maintenance of MDSCs as its linchpin; responsible for immunosuppression through the down-regulation of antitumour responses. MDSCs cause immunosuppression through a number of mechanisms; inhibiting the proliferation of CD4^+ and CD8^+ T cells, blocking natural killer cell activation and limiting dendritic cell maturation and function. As well as using various mechanisms to inhibit adaptive and immune responses, MDSCs also have non-immunological functions that aid tumour spread; including directly promoting tumour proliferation and metastasis by having an important role in tumour angiogenesis, secretion of matrix metalloproteinases and induction of epithelial-mesenchymal transition. Breast cancer is the most common cancer among women in the United Kingdom with 44540 new cases of invasive carcinoma in 2013 and results in the second highest cancer mortality rate in women, with 11600 deaths in 2012. Considering this, the need for novel therapeutic interventions is higher than ever. This review summarises the rationale for the targeting of MDSCs in breast cancer as a realistic avenue to increase survival from breast cancer.
