CD47 and FOXP3+ Regulatory Immunity in Colorectal Cancer: A Conceptual Framework for Coordinated Immunosuppression.

In colorectal cancer (CRC), tumor progression is influenced by immunosuppressive tumor microenvironment (TME), in which innate immunity and adaptive immunity play an important role. CD47 is one of the key molecules in the process. It sends a "don't eat me" signal to macrophages by binding to signal regulatory protein alpha (SIRPα), thus helping tumor cells escape immune clearance. Forkhead box P3 (FOXP3)+ regulatory immune cells further suppress antitumor T-cell responses. Here, based on a review of the literature and publicly available transcriptomic data, we propose that CD47 expression and FOXP3+ regulatory T cells in CRC are interconnected components of a broader myeloid-regulatory immunosuppressive phenotype, rather than a simple linear CD47-FOXP3 pathway. Evidence from cancer studies and exploratory GEPIA3/TIMER3.0 analyses supports a weak and method-dependent association between CD47 expression, FOXP3 transcripts, and estimated Treg infiltration. Hippo/Yes-associated protein/transcriptional coactivator with PDZ-binding motif (YAP/TAZ) signaling serves as a potential upstream program contributing to this immune context.