Antagonism of the a7nAChR exerts anti-tumor activity in metastatic colorectal cancer via expansion of C1qa positive macrophages
Metastatic colorectal cancer (mCRC) remains lethal due to limited therapeutic options. The tumor immune microenvironment (TIME) critically determines cancer progression, yet regulatory circuits remain incompletely understood. The nicotinic acetylcholine receptor a7 subunit (a7nAChR) represents an immunomodulatory target, but its role in remodeling the mCRC TIME and the identity of pharmacological regulators remain unexplored.We employed Chrna7-knockout mice and wild-type littermates in a peritoneal mCRC model (MC38 cells). Single-cell RNA sequencing identified key regulatory populations.a7nAChR deficiency increased immune infiltration, reduced tumor cell proliferation, and enhanced apoptosis. Single-cell analysis revealed selective expansion of a C1qa positive macrophage subpopulation; exogenous C1q supplementation inhibited tumor growth, confirming their functional importance.