Exosomal high-mobility group box 1 produced by HCC cells can promote Breg expansion via the TLR-MAPK signaling pathway, and TLR activation can also increase the expression of Bcl-6, which is required for HCC environmental factors to promote the formation of PD-1high Bregs [146], [163, 166–168]. The gene discussed is HMGB1; the disease is hepatocellular carcinoma.