Prognostic relevance of sarcopenia and tumor-infiltrating CD8+ T cells in patients with hepatocellular carcinoma

Abstract

Aim: The relationship between sarcopenia, tumor-infiltrating lymphocytes (TILs),and long-term survival in patients with hepatocellular carcinoma (HCC) has not beeninvestigated. We aimed to evaluate the prognostic relevance of sarcopenia and TILsin patients with HCC.Methods: We included 351 patients with HCC following liver resection. Sarcopeniawas defined based on the skeletal muscle index using computed tomography. Tumor-infiltrating CD4+ and CD8+ T cells, perforin, and granzyme B were examined in liverresection specimens. Results: Sarcopenia patients had a significantly lower lymphocyte count (p = 0.003),prognostic nutritional index (p = 0.017), and CD4+ and CD8+ T cell counts (p = 0.008and p = 0.006, respectively). The overall survival (OS) and recurrence-free survival(RFS) rates of sarcopenia patients were significantly lower than non-sarcopeniapatients (both p < 0.001). Multivariate analysis revealed that sarcopenia and lowCD8 levels were strong independent poor prognostic factors for OS and RFS (bothp < 0.001). Regardless of sarcopenia, patients with high CD8 levels had significantly better OS and RFS rates and increased expression of perforin and granzyme B.Particularly, sarcopenia patients with high CD8 levels had much better OS and RFSthan those with low CD8 levels and were even comparable to non-sarcopenia patientswith high CD8 levels.Conclusions: Sarcopenia and low CD8 levels are strong independent poor prognosticfactors in patients with HCC. Furthermore, sarcopenia patients with high CD8 levelshad favorable survival and activated local immunity, suggesting that tumor-infiltrating CD8+ T cells may play a functionally important role in sarcopenia patients.K E Y W O R D SCD8+ T cells, hepatocellular carcinoma, liver resection, sarcopenia, tumor-infiltratinglymphocytes