학술논문
Peripheral T Cell Subpopulations as a Potential Surrogate Biomarker during Atezolizumab plus Bevacizumab Treatment for Hepatocellular Carcinoma.
Document Type
Article
Author
Shirane, Yuki; Fujii, Yasutoshi; Ono, Atsushi; Nakahara, Hikaru; Hayes, Clair Nelson; Miura, Ryoichi; Murakami, Serami; Sakamoto, Naoya; Uchikawa, Shinsuke; Fujino, Hatsue; Nakahara, Takashi; Murakami, Eisuke; Yamauchi, Masami; Miki, Daiki; Kawaoka, Tomokazu; Arihiro, Koji; Tsuge, Masataka; Oka, Shiro
Source
Subject
*THERAPEUTIC use of monoclonal antibodies
*FLOW cytometry
*T cells
*PREDICTION models
*MONONUCLEAR leukocytes
*RESEARCH funding
*BEVACIZUMAB
*IMMUNOTHERAPY
*FISHER exact test
*TUMOR markers
*RETROSPECTIVE studies
*MULTIVARIATE analysis
*IMMUNOLOGIC memory
*MANN Whitney U Test
*QUANTITATIVE research
*GENE expression
*IMMUNOHISTOCHEMISTRY
*KAPLAN-Meier estimator
*LOG-rank test
*LONGITUDINAL method
*IMMUNE checkpoint inhibitors
*COMBINED modality therapy
*DRUG efficacy
*PROGRESSION-free survival
*COMPARATIVE studies
*DATA analysis software
*INFLAMMATION
*HEPATOCELLULAR carcinoma
*OVERALL survival
*PROPORTIONAL hazards models
*REGRESSION analysis
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Language
ISSN
2072-6694
Abstract
Simple Summary: In this study, we evaluated the status and dynamics of peripheral T cell subpopulations in hepatocellular carcinoma (HCC) patients receiving immune checkpoint blockade with atezolizumab plus bevacizumab (Atez/Bev) treatment and explored biomarkers that are predictive of therapeutic response. The results showed that a higher proportion of CD8+ central memory T cells at baseline is associated with tumor inflammation in HCC, as well as with longer progression-free survival in response to Atez/Bev treatment, especially in cases with an increased proportion of CD8+ effector memory T cells after 3 weeks. Our findings suggest that the peripheral T cell subpopulation can serve as a potential noninvasive biomarker predicting benefits from Atez/Bev treatment. 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. [ABSTRACT FROM AUTHOR]