Peripheral T Cell Subpopulations as a Potential Surrogate Biomarker during Atezolizumab plus Bevacizumab Treatment for Hepatocellular Carcinoma

Yuki Shirane; Yasutoshi Fujii; Atsushi Ono; Hikaru Nakahara; Clair Nelson Hayes; Ryoichi Miura; Serami Murakami; Naoya Sakamoto; Shinsuke Uchikawa; Hatsue Fujino; Takashi Nakahara; Eisuke Murakami; Masami Yamauchi; Daiki Miki; Tomokazu Kawaoka; Koji Arihiro; Masataka Tsuge; Shiro Oka

doi:10.3390/cancers16071328

Cancers (Mar 2024)

Peripheral T Cell Subpopulations as a Potential Surrogate Biomarker during Atezolizumab plus Bevacizumab Treatment for Hepatocellular Carcinoma

Yuki Shirane,
Yasutoshi Fujii,
Atsushi Ono,
Hikaru Nakahara,
Clair Nelson Hayes,
Ryoichi Miura,
Serami Murakami,
Naoya Sakamoto,
Shinsuke Uchikawa,
Hatsue Fujino,
Takashi Nakahara,
Eisuke Murakami,
Masami Yamauchi,
Daiki Miki,
Tomokazu Kawaoka,
Koji Arihiro,
Masataka Tsuge,
Shiro Oka

Affiliations

Yuki Shirane: Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
Yasutoshi Fujii: Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
Atsushi Ono: Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
Hikaru Nakahara: Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
Clair Nelson Hayes: Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
Ryoichi Miura: Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
Serami Murakami: Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
Naoya Sakamoto: Division of Pathology, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Kashiwa, Chiba 277-8577, Japan
Shinsuke Uchikawa: Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
Hatsue Fujino: Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
Takashi Nakahara: Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
Eisuke Murakami: Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
Masami Yamauchi: Department of Clinical Oncology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
Daiki Miki: Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
Tomokazu Kawaoka: Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
Koji Arihiro: Department of Anatomical Pathology, Hiroshima University Hospital, Hiroshima 734-8551, Japan
Masataka Tsuge: Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
Shiro Oka: Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan

DOI: https://doi.org/10.3390/cancers16071328
Journal volume & issue: Vol. 16, no. 7
p. 1328

Abstract

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The therapeutic benefits of the immunotherapeutic combination of atezolizumab and bevacizumab (Atez/Bev) in hepatocellular carcinoma (HCC) vary. Therapeutic biomarkers might help improve outcomes for HCC patients receiving Atez/Bev therapy. The role of systemic immune profiles in HCC progression also remains unclear. This study aimed to evaluate the status and dynamics of peripheral T cell subpopulations in HCC patients receiving Atez/Bev treatment and to explore biomarkers predictive of a therapeutic response. We enrolled 83 unresectable advanced HCC patients who commenced Atez/Bev treatment at our hospital between October 2020 and June 2022. Peripheral T cell subpopulations in peripheral blood mononuclear cells at baseline and 3 weeks post-treatment were investigated using flow cytometry and compared with those in control samples from 18 healthy individuals. We retrospectively analyzed the association between peripheral T cell subpopulation profiles and clinical outcomes. Baseline peripheral T cell subpopulations could be profiled in 70 patients with sufficient cell counts, among whom 3-week subpopulations could be evaluated in 51 patients. Multivariate analysis showed that a high baseline proportion of CD8+ central memory T (TCM) cells was independently associated with longer progression-free survival (PFS). Further, overall survival (OS) was significantly prolonged in patients with increased CD8+ effector memory T (TEM) cell proportions. In conclusion, TCM proportion at baseline might be a good indicator of the efficacy of Atez/Bev therapy. Furthermore, observation of increasing TEM proportions might be an early predictor of the potential clinical benefits of treatment.

Published in Cancers

ISSN: 2072-6694 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.mdpi.com/journal/cancers/

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