Enhanced formation of tertiary lymphoid structures shapes the anti-tumor microenvironment in hepatocellular carcinoma after FOLFOX-HAIC therapy.

ABSTRACT: Tertiary lymphoid structures (TLSs) emerge as crucial determinants of anti-tumor immune responses and clinical outcomes. However, their clinical significance and formation mechanisms in hepatocellular carcinoma (HCC) remain unclear. Here, we demonstrate that hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin, leucovorin, and fluorouracil (FOLFOX) significantly enhances TLS formation in HCC tissues, correlating with improved therapeutic efficacy and prolonged progression-free survival in patients with HCC. Mechanistically, HAIC induces lymphotoxin β (LTβ)-expressing central memory T cell (T_CM)-like CD4⁺ T cells, which activate MMP2⁺ fibroblasts and FOLR2⁺CCL4⁺ macrophages via the LTβ-LTβR axis to drive TLS development. Furth

SUBMITTER: Xing R 

PROVIDER: S-EPMC12490226 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature