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 been investigated. We aimed to evaluate the prognostic relevance of sarcopenia and TILs in patients with HCC. Methods We included 35...

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Main Authors: Shunsuke Doi, Satoshi Yasuda, Miu Miyashita, Minako Nagai, Kota Nakamura, Yasuko Matsuo, Taichi Terai, Yuichiro Kohara, Takeshi Sakata, Masayuki Sho
Format: Article
Language:English
Published: Wiley 2025-03-01
Series:Annals of Gastroenterological Surgery
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Online Access:https://doi.org/10.1002/ags3.12875
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author Shunsuke Doi
Satoshi Yasuda
Miu Miyashita
Minako Nagai
Kota Nakamura
Yasuko Matsuo
Taichi Terai
Yuichiro Kohara
Takeshi Sakata
Masayuki Sho
author_facet Shunsuke Doi
Satoshi Yasuda
Miu Miyashita
Minako Nagai
Kota Nakamura
Yasuko Matsuo
Taichi Terai
Yuichiro Kohara
Takeshi Sakata
Masayuki Sho
author_sort Shunsuke Doi
collection DOAJ
description 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.
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spelling doaj-art-78a165341f03411e98dc11deb88af2ee2025-08-20T03:16:24ZengWileyAnnals of Gastroenterological Surgery2475-03282025-03-019235936810.1002/ags3.12875Prognostic relevance of sarcopenia and tumor‐infiltrating CD8+ T cells in patients with hepatocellular carcinomaShunsuke Doi0Satoshi Yasuda1Miu Miyashita2Minako Nagai3Kota Nakamura4Yasuko Matsuo5Taichi Terai6Yuichiro Kohara7Takeshi Sakata8Masayuki Sho9Department of Surgery Nara Medical University Nara JapanDepartment of Surgery Nara Medical University Nara JapanDepartment of Surgery Nara Medical University Nara JapanDepartment of Surgery Nara Medical University Nara JapanDepartment of Surgery Nara Medical University Nara JapanDepartment of Surgery Nara Medical University Nara JapanDepartment of Surgery Nara Medical University Nara JapanDepartment of Surgery Nara Medical University Nara JapanDepartment of Surgery Nara Medical University Nara JapanDepartment of Surgery Nara Medical University Nara JapanAbstract 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.https://doi.org/10.1002/ags3.12875CD8+ T cellshepatocellular carcinomaliver resectionsarcopeniatumor‐infiltrating lymphocytes
spellingShingle Shunsuke Doi
Satoshi Yasuda
Miu Miyashita
Minako Nagai
Kota Nakamura
Yasuko Matsuo
Taichi Terai
Yuichiro Kohara
Takeshi Sakata
Masayuki Sho
Prognostic relevance of sarcopenia and tumor‐infiltrating CD8+ T cells in patients with hepatocellular carcinoma
Annals of Gastroenterological Surgery
CD8+ T cells
hepatocellular carcinoma
liver resection
sarcopenia
tumor‐infiltrating lymphocytes
title Prognostic relevance of sarcopenia and tumor‐infiltrating CD8+ T cells in patients with hepatocellular carcinoma
title_full Prognostic relevance of sarcopenia and tumor‐infiltrating CD8+ T cells in patients with hepatocellular carcinoma
title_fullStr Prognostic relevance of sarcopenia and tumor‐infiltrating CD8+ T cells in patients with hepatocellular carcinoma
title_full_unstemmed Prognostic relevance of sarcopenia and tumor‐infiltrating CD8+ T cells in patients with hepatocellular carcinoma
title_short Prognostic relevance of sarcopenia and tumor‐infiltrating CD8+ T cells in patients with hepatocellular carcinoma
title_sort prognostic relevance of sarcopenia and tumor infiltrating cd8 t cells in patients with hepatocellular carcinoma
topic CD8+ T cells
hepatocellular carcinoma
liver resection
sarcopenia
tumor‐infiltrating lymphocytes
url https://doi.org/10.1002/ags3.12875
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