Bacillus Calmette-Guerin induces CD8+ T cell infiltration and suppresses tumor progression in microsatellite stable colorectal cancer by downregulating ARID1A.

Abstract

Neoadjuvant immunotherapy demonstrates limited efficacy in microsatellite-stable (MSS) colorectal cancer (CRC). In vivo observations reveal that Bacillus Calmette-Guérin (BCG) can inhibit the progression of MSS-CRC and downregulate ARID1A in both in vivo and in vitro settings. Through the analysis of clinical samples, in vivo and in vitro models, and bioinformatics, we found that the low expression of ARID1A promotes tumor growth in vitro; however, in vivo, it enhances CD8+ T cell infiltration in MSS-CRC tissues while inhibiting tumor growth. Further investigation revealed that BCG downregulates ARID1A via the TLR4/NF-κB pathway, leading to the downregulation of MLH1 and PMS2 and subsequent alterations in MMR function in MSS-CRC. This cascade enhances antigen presentation, promotes CD8+ T cell infiltration, and contributes to tumor suppression.