Interaction Between Immunosuppressive and Cholinergic Markers in Colorectal Cancer

Colorectal cancer (CRC) is amongst the leading diagnosed cancers worldwide. Despite the increasing interest to understand, the roles that the nervous and immune systems play in influencing the tumour microenvironment to promote cancer development and progression, more studies are required to understand the mechanism. Cancer cells can influence their microenvironment and bi-directionally communicate with other systems such as the immune and nervous systems. The immune system plays a key role in the eradication of cancer cells. Studies have shown that multiple mechanisms are responsible for the suppression of the immune system in cancer, one of which being the expression of immune checkpoints inhibitors such as programmed death 1 (PD-1), PD-L1, programmed death ligand 1 and 2 (PD-L1, PD- L2), sialic acid-binding lectins 9 (siglec-9) and IDO (indoleamine-2,3-dioxygenase). These molecules function by inhibiting anti-tumour effects of T cell-mediated immune responses. In addition to these molecules, studies have shown that several cancers can release acetylcholine (ACh) and express cholinergic receptors (muscarinic receptor 3 (M3R) and alpha 7 nicotinic receptor (a7nAChR)), overexpress choline acetyltransferase (ChAT), a precursor enzyme required for ACh synthesis and VAChT, essential for transporting of ACh, and excitatory receptor. Currently, there are no data available in determining the interaction between the expression of immunosuppressive and cholinergic markers in cancer, thus, this thesis aims to determine the interaction between the expression of immunosuppressive and cholinergic markers in CRC.