Observational Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 28, 2023; 29(40): 5582-5592
Published online Oct 28, 2023. doi: 10.3748/wjg.v29.i40.5582
Expression characteristics of peripheral lymphocyte programmed death 1 and FoxP3+ Tregs in gastric cancer during surgery and chemotherapy
Hao Li, Guan-Mei Cao, Guo-Li Gu, Song-Yan Li, Yang Yan, Ze Fu, Xiao-Hui Du
Hao Li, Ze Fu, Graduate School, Medical School of Chinese People’s Liberation Army, Beijing 100039, China
Hao Li, Guo-Li Gu, Department of General Surgery, Air Force Medical Center, Air Force Medical University, Beijing 100142, China
Guan-Mei Cao, Department of Radiology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China
Song-Yan Li, Yang Yan, Xiao-Hui Du, Department of General Surgery, Chinese PLA General Hospital, Beijing 100039, China
Co-first authors: Hao Li and Guan-Mei Cao.
Author contributions: Li H, Cao GM, and Du XH were the guarantor of integrity of entire study, and contributed to the study concepts; Li H, Cao GM, Gu GL, Li SY, and Du XH designed the study; Li H, Cao GM, Gu GL, and Li SY involved in the literature research; Li H and Cao GM contributed to the data acquisition; Li H, Cao GM, and Fu Z contributed to the statistical analysis/interpretation and manuscript preparation; Li H, Cao GM, Gu GL, Li SY, Fu Z, and Du XH contributed to the manuscript definition of intellectual content; Li H, Cao GM, Gu GL, and Du XH edited the manuscript; Li H and Cao GM contributed equally to this work as co-first authors; Li H and Cao GM are designated as co-first authors due to their equal and substantial contributions to the study conception, design, data acquisition, and analysis, as well as manuscript preparation and editing, each playing pivotal roles in ensuring the integrity and quality of the research.
Supported by the National Natural Science Foundation of China, No. 81871317; and Military Medical Innovation Project, No. 18CXZ025.
Institutional review board statement: The study was reviewed and approved by the Ethics Commission of the General Hospital of PLA (Approval No. S2009-051-02).
Informed consent statement: All patients and donors provided signed informed consent.
Conflict-of-interest statement: There are no conflicts of interest to report.
Data sharing statement: The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Xiao-Hui Du, MD, PhD, Chief Doctor, Deputy Director, Professor, Surgeon, Department of General Surgery, Chinese PLA General Hospital, No. 28 Fuxing Road, Haidian District, Beijing 100039, China. duxiaohui3011@sina.com
Received: August 7, 2023
Peer-review started: August 7, 2023
First decision: August 28, 2023
Revised: August 31, 2023
Accepted: October 11, 2023
Article in press: October 11, 2023
Published online: October 28, 2023
Processing time: 81 Days and 6.4 Hours
Abstract
BACKGROUND

Programmed death 1 (PD-1) and CD4+CD25+FoxP3+ expression in peripheral blood T-cells has been previously reported in various types of cancer. However, the specific variation tendency during surgery and chemotherapy, as well as their relationship in gastric cancer patients, still remain unclear. Understanding this aspect may provide some novel insights for future studies on tumor recurrence and tumor immune escape, and also serve as a reference for determining the optimal timing and dose of clinical anti-PD-1 antibodies.

AIM

To observe and analyze the expression characteristics of peripheral lymphocyte PD-1 and FoxP3+ regulatory T cells (FoxP3+ Tregs) before and after surgery or chemotherapy in gastric cancer patients.

METHODS

Twenty-nine stomach cancer patients undergoing chemotherapy after a D2 gastrectomy provided 10 mL peripheral blood samples at each phase of the perioperative period and during chemotherapy. This study also included 29 age-matched healthy donors as a control group. PD-1 expression was detected on lymphocytes, including CD4+CD8+CD45RO+, CD4+CD45RO+, and CD8+CD45RO+ lymphocytes as well as regulatory T cells.

RESULTS

We observed a significant increase of PD-1 expression on immune subsets and a larger number of FoxP3+ Tregs in gastric cancer patients (P < 0.05). Following D2 gastrectomy, peripheral lymphocytes PD-1 expression and the number of FoxP3+ Tregs notably decrease (P < 0.05). However, during postoperative chemotherapy, we only observed a decrease in PD-1 expression on lymphocytes in the CD8+CD45RO+ and CD8+CD45RO+ populations. Additionally, linear correlation analysis indicated a positive correlation between PD-1 expression and the number of CD4+CD45RO+FoxP3high activated Tregs (aTregs) on the total peripheral lymphocytes (r = 0.5622, P < 0.0001).

CONCLUSION

The observed alterations in PD-1 expression and the activation of regulatory T cells during gastric cancer treatment may offer novel insights for future investigations into tumor immune evasion and the clinical application of anti-PD-1 antibodies in gastric cancer.

Keywords: Programmed death 1; Active regulatory T cells; Stomach cancer; Peripheral lymphocyte

Core Tip: In short, this paper shows that programmed death 1 (PD-1) expression on immune subsets and the number of FoxP3+ Treg were higher in peripheral blood of patients with gastric cancer than healthy donors. PD-1 expression and the number of FoxP3+ Treg decrease notably after D2 gastrectomy. PD-1 expression declines on lymphocytes, CD8+, CD45RO+ and CD8+CD45RO+ populations during postoperative chemotherapy. PD-1 expression correlates with the number of CD4+CD45RO+FoxP3 high activated Treg in peripheral lymphocytes. This paper is particularly timely, as the studies of PD-1 expression on immune subsets in peripheral blood are of expanding interest. As well as providing some novel insight for future studies of tumor recurrence and tumor immune escape, our results might also be a reference to determining the timing and dose of clinical anti-PD-1 antibodies, and we anticipate that this study will be widely cited.