한빛사논문
- 조회67
가톨릭대학교 의과대학
Ji Won Han1,2,3+, Min Woo Kang1,3+, Soon Kyu Lee1,4, Hyun Yang1,5, Ji Hoon Kim1,6, Jae-Sung Yoo1,2, Hee Sun Cho1,2, Eun Ji Jang1,3, Deok Hwa Seo1,3, Jung Hyun Kwon1,4, Soon Woo Nam1,4, Si Hyun Bae1,5, Jeong Won Jang1,2, Jong Young Choi1,2, Seung Kew Yoon1,2, Pil Soo Sung1,2,3*
1The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
2Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul 06591, Republic of Korea
3Catholic University of Korea College of Medicine, Department of Biomedicine & Health Sciences, POSTECH-Catholic Biomedical Engineering Institute, Seoul 06591, Republic of Korea
4Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Incheon St. Mary’s Hospital, The Catholic University of Korea, Incheon 22711, Republic of Korea
5Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Eunpyeong St. Mary’s Hospital, The Catholic University of Korea, Seoul 03382, Republic of Korea
6Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Uijeongbu St. Mary’s Hospital, The Catholic University of Korea, Uijeongbu 11765, Republic of Korea
+Co-first authors
Corresponding Author: Pil Soo Sung, M.D., Ph.D.
Abstract
Introduction: Variability in response to atezolizumab plus bevacizumab (AB) treatment of hepatocellular carcinoma (HCC) underscores the critical need for the development of effective biomarkers. We sought to identify peripheral blood biomarkers reflecting response to AB treatment.
Methods: We analyzed dynamic changes in peripheral blood mononuclear cells from a prospective, multicenter cohort of 65 patients with HCC, using flow cytometry to evaluate the T-cell population before and 3 weeks after the first AB treatment.
Results: We found a unique response of the CD8+ T cells in terms of both frequency and phenotype, in contrast to CD4+ T cells and regulatory T cells. Notably, CD8+ T cells showed significant changes in expression of Ki-67 and T-cell immunoreceptors with Ig and ITIM domains (TIGIT). These distinct responses were observed particularly in the programmed cell death receptor-1 (PD-1)+ subpopulation of CD8+ T cells. Interestingly, the baseline differentiation status of PD-1+CD8+ T cells, particularly the central memory T-cell subset, correlated positively with greater proliferation (higher Ki-67 expression) of PD-1+CD8+ T cells after treatment. Moreover, effector memory cells expressing CD45RA correlated negatively with the increase in TIGIT+/PD-1+CD8+ T cells. The increase in TIGIT+/CD8+ T cells was associated with the development of immune-related adverse events, whereas increase in Ki-67+/PD-1+CD8+ T cells was associated with the better objective response rate. Importantly, dynamic shifts of Ki-67+/PD-1+CD8+ T cells and TIGIT+/CD8+ T cells significantly predicted progression-free survival and overall survival, as confirmed by multivariate analysis.
Conclusion: These findings highlight the potential of dynamic changes in CD8+ T cells as an on-treatment prognostic biomarker. Our study underscores the value of peripheral blood profiling as a noninvasive and practical method for predicting the clinical outcomes of AB treatment in patients with HCC.
논문정보
- Research article
- 2024년 09월 (BRIC 등록일 2024-09-03)
- 국내 연구진
- 의약학 > 면역의학
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