The Complex Interaction between the Tumor Micro-Environment and Immune Checkpoints in Breast Cancer

Abstract

The progression of breast cancer and its association with clinical outcome and treatment remain largely unexplored. Accumulating data has highlighted the interaction between cells of the immune system and the tumor microenvironment in cancer progression, and although studies have identified multiple facets of cancer progression within the development of the tumor microenvironment (TME) and its constituents, there is lack of research into the associations between breast cancer subtype and staging. Current literature has provided insight into the cells and pathways associated with breast cancer progression through expression analysis. However, there is lack of co-expression studies between immune pathways and cells of the TME that form pro-tumorigenic relationships contributing to immune-evasion. We focus on the immune checkpoint and TME elements that influence cancer progression, particularly studies in molecular subtypes of breast cancer.

Crosstalk between Tumor Cells and Immune System Leads to Epithelial-Mesenchymal Transition Induction and Breast Cancer Progression

“…A strong correlation presents between N2 TAN in the TME and breast cancer subtypes, as TANs are predominantly observed in TNBC subtype of breast cancer [3] . Consistently, a high expression level of TGFβ was observed in TNBC contributing to the neutrophil chemotaxis; however, TGF-β may also induce a pro-tumorigenic N2 TAN phenotype [3] .…”

“…Comprehensive understanding of the TME of breast cancer has revealed strong evidence to propose that TME and the associated molecules contribute to the development of tumor growth and metastasis. The critical elements of TME in breast cancer may help us to discover the new biomarkers, including immunological and immunosuppressive markers with a function in tumor progression [3] . In this context, the role of immune cells in EMT have been well studied [4,5] .…”

“…J. 25 (1): [1][2][3][4][5][6][7] vimentin, fibronectin, and N-cadherin [6,7] . Indeed, EMT is the main cause of heterogeneity of carcinoma cells, resulting in the alteration of their biological functions and phenotypic characteristics [8] .…”

Opportunities for Conventional and In Situ Cancer Vaccine Strategies and Combination with Immunotherapy for Gastrointestinal Cancers, A Review

“…Suppressive mechanisms however may limit the effect of vaccination. Tumors actively keep the immune system at bay by shielding themselves from the outside with a thick stroma or fibrotic shell [24], an anti-inflammatory microenvironment containing immune suppressive cells like M2-macrohpages [25], regulatory T cells [26], myeloid derived suppressor cells (MDSCs) [27], or by utilizing immune pathways like the PD1-PDL1 axis to suppress responses [28][29][30]. For gastrointestinal cancers these anti-cancer immune suppressing mechanisms show substantial redundancy as in situ approaches to enhance immune system activity through local application of non-relevant vaccines (e.g., anti-rotaviral vaccines or anti-yellow fever vaccines) only generate local immune responses to cancer when combined with ICB [31,32].…”

Cancer Vaccines: Research and Applications

“…As a result, these elements create a microenvironment favorable for tumor progression, and the tumor is able to escape from the host’s immune system. It is important when designing cancer vaccines that there is clear knowledge of a tumor’s microenvironment and immunosuppressive factors, as these will greatly influence the outcome of immune therapeutic approaches [7].…”