Investigation of the impact of LG2m on the tumor immune microenvironment and the efficacy of cancer immunotherapy in hepatocellular carcinoma

Research has been progressing to identify factors associated with the therapeutic efficacy of cancer immunotherapy for hepatocellular carcinoma (HCC). In this study, we analyzed the impact of laminin γ2 monomer (LG2m), a serum marker of CD90-positive HCC, a mesenchymal cancer cell subtype previously reported as a predictive biomarker for liver carcinogenesis, on the tumor immune microenvironment and its effect on cancer immunotherapy efficacy. Multiplex spatial analysis revealed that LG2m-high HCC exhibited lower intratumoral lymphocyte infiltration. At the tumor border, CD90-positive cells and CD206-positive macrophages were abundant, while Ki67-positive activated CD4- and CD8-positive T cell infiltration was limited. Cellular Neighborhood analysis showed enrichment of CD90-positive cells at the tumor border with poor proximity to Ki67-positive activated T cells. These findings suggest LG2m-high HCC suppresses antitumor immune T cell infiltration or activation.
To complement these findings, we compared the efficacy of atezolizumab plus bevacizumab versus sorafenib in HCC patients stratified by LG2m expression. In the LG2m-low group, atezolizumab plus bevacizumab significantly improved progression-free survival (PFS) compared to sorafenib (HR 0.33, P < 0.001). However, in the LG2m-high group, no significant PFS benefit was observed (HR 0.65, P = 0.15).
In conclusion, LG2m-high HCC is associated with an immunosuppressive tumor microenvironment and poor response to cancer immunotherapy.