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. 2024 Oct 26;9(2):359-368.
doi: 10.1002/ags3.12875. eCollection 2025 Mar.

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

Shunsuke Doi  1 , Satoshi Yasuda  1 , Miu Miyashita  1 , Minako Nagai  1 , Kota Nakamura  1 , Yasuko Matsuo  1 , Taichi Terai  1 , Yuichiro Kohara  1 , Takeshi Sakata  1 , Masayuki Sho  1
Affiliations

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

Shunsuke Doi et al. Ann Gastroenterol Surg. .

Abstract

Aim: The relationship between sarcopenia, tumor-infiltrating lymphocytes (TILs), and long-term survival in patients with hepatocellular carcinoma (HCC) has not been investigated. We aimed to evaluate the prognostic relevance of sarcopenia and TILs in patients with HCC.

Methods: We included 351 patients with HCC following liver resection. Sarcopenia was defined based on the skeletal muscle index using computed tomography. Tumor-infiltrating CD4+ and CD8+ T cells, perforin, and granzyme B were examined in liver resection 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 = 0.008 and p = 0.006, respectively). The overall survival (OS) and recurrence-free survival (RFS) rates of sarcopenia patients were significantly lower than non-sarcopenia patients (both p < 0.001). Multivariate analysis revealed that sarcopenia and low CD8 levels were strong independent poor prognostic factors for OS and RFS (both p < 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 RFS than those with low CD8 levels and were even comparable to non-sarcopenia patients with high CD8 levels.

Conclusions: Sarcopenia and low CD8 levels are strong independent poor prognostic factors in patients with HCC. Furthermore, sarcopenia patients with high CD8 levels had favorable survival and activated local immunity, suggesting that tumor-infiltrating CD8+ T cells may play a functionally important role in sarcopenia patients.

Keywords: CD8+ T cells; hepatocellular carcinoma; liver resection; sarcopenia; tumor‐infiltrating lymphocytes.

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Conflict of interest statement

Prof. Masayuki Sho is an editorial board member of Annals of Gastroenterological Surgery. The authors declare no conflicts of interest for this article.

Figures

FIGURE 1
FIGURE 1
Representative images of TILs in HCC. (A) High‐CD4 group; (B) High‐CD8 group; (C) Low‐CD4 group; (D) Low‐CD8 group. HCC, hepatocellular carcinoma; TILs, tumor‐infiltrating lymphocytes.
FIGURE 2
FIGURE 2
(A), (B) Overall and recurrence‐free survival of the patients in the sarcopenia and non‐sarcopenia groups (p < 0.001 for both).
FIGURE 3
FIGURE 3
(A), (B) Overall and recurrence‐free survival based on sarcopenia and tumor‐infiltrating CD8+ T cells. *Statistically significant difference at p < 0.05.
FIGURE 4
FIGURE 4
(A), (B) The expressions of perforin and granzyme B in HCC tissue by qRT‐PCR analysis according to sarcopenia and CD8+ T cells. *Statistically significant difference at p < 0.05. qRT‐PCR, quantitative reverse transcription polymerase chain reaction; HCC, hepatocellular carcinoma.
See this image and copyright information in PMC

References

    1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–249. - PubMed
    1. Vogel A, Meyer T, Sapisochin G, Salem R, Saborowski A. Hepatocellular carcinoma. Lancet. 2022;400(10360):1345–1362. - PubMed
    1. Ban D, Ogura T, Akahoshi K, Tanabe M. Current topics in the surgical treatments for hepatocellular carcinoma. Ann Gastroenterol Surg. 2018;2(2):137–146. - PMC - PubMed
    1. Yoh T, Ishii T, Nishio T, Koyama Y, Ogiso S, Fukumitsu K, et al. A conceptual classification of resectability for hepatocellular carcinoma. World J Surg. 2023;47(3):740–748. - PMC - PubMed
    1. Marrero JA, Kulik LM, Sirlin CB, Zhu AX, Finn RS, Abecassis MM, et al. Diagnosis, staging, and Management of Hepatocellular Carcinoma: 2018 practice guidance by the American Association for the Study of Liver Diseases. Hepatology. 2018;68(2):723–750. - PubMed