Expression characteristics of peripheral lymphocyte programmed death 1 and FoxP3+ Tregs in gastric cancer during surgery and chemotherapy

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⁺FoxP3^high 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.

Key Words: 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.

INTRODUCTION

Global cancer statistics have revealed that there were 1089103 newly diagnosed gastric cancer cases in 2020, resulting in a significant number of newly diagnosed gastric cancer cases and deaths worldwide[1]. Specifically, the National Cancer Centre of China estimated that 679000 new gastric cancer cases and 498000 gastric cancer-related deaths would occur in China in 2015[2]. Further compounding this issue is the fact that almost 70% of newly diagnosed cases are advanced gastric cancer, with the overall five-year survival rate being less than 30%[3].

With the advances of Chimeric antigen receptor T-cells, genetically engineered T cells, cytotoxic T-lymphocyte-associated antigen-4, and the programmed death-1/programmed death-ligand (PD-1/PD-L) pathway, tumor immunotherapy has rapidly emerged as a field of advanced research[4].

Multiple clinical trials have confirmed the efficacy and safety of PD-1 monoclonal antibody[5,6], and PD-1 monoclonal antibody was already approved for advanced gastric cancer in the United States and Japan. However, a recently randomized and open Phase III trial, Keymat-61[7], showed no significant improvement on objective response rate or progression-free survival (PFS) from paclitaxel. Meanwhile, in the randomized III trials, JAVELIN Gastric 300, reported by Bang et al[8], Avelumab in the treatment of advanced gastric/gastroesophageal joint cancer patients did not improve OS and PFS compared with the third-line treatment.

A growing body of evidence suggests that Tregs might be involved in the treatment of PD-1/PD-L1 blockade and PD-1/PD-L1 axis could influence Treg differentiation and function. However, the complex relationship between PD-1/PD-L1 pathway and Tregs is yet to be fully elucidated[9,10].

Although research into peripheral PD-1 expression in patients with gastric cancer has been reported previously, few studies have sequentially investigated such expression from the time of surgery to the completion of postoperative chemotherapy[11]. Furthermore, studies investigating the relationship between peripheral PD-1 expression and FoxP3⁺ Tregs in gastric cancer patients are largely lacking.

In this study, we detected PD-1 expression on peripheral blood T cell subsets and the population of FoxP3⁺ Tregs in gastric cancer from surgery to the completion of postoperative chemotherapy to analyse how these indexes change in expectation of being helpful to decide when and how the anti-PD-1 antibodies should be applied and deeper under-standing on the mechanism of tumor immune escape in gastric cancer in the future.

MATERIALS AND METHODS

Human subjects

Patients with a histologically confirmed diagnosis of gastric adenocarcinoma following a D2 gastrectomy and treated with postoperative adjuvant chemotherapy, as well as age-matched healthy donors were eligible for this prospective observational study. Other inclusion criteria consisted of: (1) A healthy physical examination of the donors performed within the past three months; and (2) the age of patients and donors within the range of 18-75 years old. The exclusion criteria consisted of: (1) Patients diagnosed with other types of cancer within five years; (2) patients that received preoperative adjuvant chemotherapy, radiotherapy, or immunotherapy; (3) patients and donors who were diagnosed with chronic hepatitis, human immunodeficiency virus, syphilis, or any other acute infectious disease; (4) patients and donors who suffered from rheumaimmune systemic diseases (e.g., systemic lupus erythematosus or hyperthyroidism); (5) patients with any other severe disease that might render them incapable of completing the entire course of chemotherapy; and (6) patients suffered gastric cancer recurrence or failed to finish the entire course of chemotherapy.

At the beginning of this study, 33 patients (alongside 33 age-matched donors) were enrolled from February 2020 to February 2021 in the Chinese People’s Liberation Army General Hospital (PLAGH). However, one patient experienced tumor recurrence and three who failed to complete the entire cycles were excluded. A total of 29 patients (15 men and 14 women; mean age: 59.72 years) and 29 age-matched donors (17 men and 12 women; mean age: 59.62 years) were ultimately included in this study.

This study received approval from the ethics commission of the General Hospital of PLA, and all patients and donors provided signed informed consent.

Treatment strategy for patients

The treatment strategy for the enrolled patients consisted of MDT and a D2 gastrectomy performed by a chief physician at the General Hospital of PLA. The patients were treated with the following doses of chemotherapy and affiliated schedules: Oral capecitabine (1000 mg/m² twice daily on days 1-14 of each cycle) plus intravenous oxaliplatin (130 mg/m² on day 1 of each cycle) for eight three-week cycles.

Flow cytometry analysis

A sample volume of 10 mL peripheral blood was obtained from the patients into ananticoagulation tube on the day before surgery, the first and fourth cycles of chemotherapy and the day after chemotherapy. All blood samples were analysed within 6 h. Each sample was divided into two tubes and the detection of PD-1 expression and CD4⁺CD25⁺FoxP3⁺ regulatory T cells was performed separately on Accuri C6, a four-channel flow cytometer form BD ACCURI (Franklin Lakes, NJ, United States).

The detection of PD-1 expression involved staining the cells from the whole blood with fluorescently labelled antibodies, including anti-CD4-PerCP-Cy5.5 (clone RPA-4), anti-CD8-FITC (clone RPA-T8), anti-CD45RO-PE (clone UCHL-1) and anti-CD279 (PD-1)-APC (clone MIH4), from BD Biosciences (Franklin Lakes, NJ, United States) for the detection of PD-1 expression.

The detection of CD4⁺CD25⁺FoxP3⁺ regulatory T cells was performed by staining PBMCs with anti-CD3-APC (clone SP34-2), anti-CD4-Percp (clone RPA-T4), anti-CD25-FITC (clone M-A251) andanti-CD45RO-PE (clone UCHL-1) from BD Biosciences (Franklin Lakes, NJ, United States) first, followed by anti-FoxP3-PE (clone 236A/E7, BD Biosciences) was added after permeabilizing the cell and nuclear membranes.

Statistical analysis

Data in this paper is represented as the mean ± SD. Comparisons of the differences in the continuous variables between the patients and donors were made using a Student’s t-test or Wilcoxon rank sum test. A Chi-square test was performed for the categorical data. A paired-t test was adopted to compare the measurement data before and after the operation. Changes in the measurement data during chemotherapy were evaluated by an analysis of variance repeated-measures function. A Pearson correlation analysis was applied to dispose of the relativity between PD-1 expression and a population of FoxP3⁺ Tregs. P values were based on two-tailed tests, with a value of P < 0.05 considered to be statistically significant.

RESULTS

Human characteristics

Statistical analysis revealed no significant difference in age (59.72 ± 15.33 vs 59.62 ± 15.64, P = 0.9798), gender (15/14 vs 17/12, P = 0.7918), and body mass index (23.90 ± 5.00 vs 25.10 ± 3.18, P = 0.2824) between the patients and healthy donors. We also assessed the daily life activity of both patients and donors using the Karnofsky score; all patients scored above 60 (indicating occasional care required for most needs), which is a score above the threshold at which patients with advanced gastric cancer are advised to transition from systemic therapy to supportive therapy according to the NCCN Guidelines. The descriptive statistics for CEA levels, TNM stages, and tumor differentiation are detailed in Table 1.

Table 1 Characteristics of patients and donors.

Characteristics	Patients (n = 29)	Donors (n = 29)
Age (mean ± SD)	59.72 ± 15.33	59.62 ± 15.641
Sex (M/F)	15/14	17/121
BMI (kg/m2, mean ± SD)	23.90 ± 5.00	25.10 ± 3.181
KPs score
≥ 60	29	291
< 60	0	0
CEA (μg/L, mean ± SD)	95.26 ± 58.06	-
TNM stage		-
I	2
II	12
III	15
Differentiation		-
High	2
Moderate	18
Low	9

¹The donors exhibited no differences from the patients at P > 0.05.

BMI: Body mass index; CEA: Carcinoembryonic antigen; KPs: Karnofsky performance status.

PD-1 expression between preoperative patients and donors

We performed an analysis of PD-1 expression on fresh peripheral blood sample subsets using flow cytometry (Figure 1A). The PD-1 expression on lymphocytes obtained from patients was significantly higher than those derived from donors (22.37% ± 10.35% vs 11.77% ± 6.67%, P < 0.0001; Figure 1B-G). Similarly, PD-1 expression on the CD4⁺ and CD8⁺ lymphocytes was notably higher in the patient group compared to the donor group (7.10% ± 3.27% vs 4.18% ± 2.53%, P = 0.0004; 11.63% ± 7.06% vs 5.71% ± 3.74%, P = 0.001; Figure 1B-G). Further, we assessed the PD-1 expression in lymphocytes through CD45RO phenotyping, a crucial marker utilized to distinguish memory T cells from naive T cells. This analysis revealed a significant difference between the patients and donors (13.94% ± 6.75% vs 6.71% ± 3.86%, P < 0.0001; Figure 1B-G). Moreover, PD-1 expression on CD4⁺CD45RO⁺ and CD8⁺CD45RO⁺ lymphocytes was also markedly higher in the gastric cancer patients (5.16% ± 2.31% vs 2.67% ± 1.57%, P < 0.0001; 8.79% ± 5.15% vs 4.05% ± 2.67%, P < 0.0001; Figure 1B-G).

Figure 1 Programmed death 1 expression on all T cell subsets of healthy donors and preoperative patients with gastric cancer. A: The scatter and histogram plots of one representative patient are illustrated. The relationships between the diagrams are indicated by arrows and gates (R1, R2, and R3); B-G: The percentages of total programmed death 1⁺ (PD-1⁺) cells (B), CD4⁺PD-1⁺ (C), CD8⁺PD-1⁺ (D), CD45RO⁺PD-1⁺ (E), CD4⁺CD45RO⁺PD-1⁺ (F), and CD8⁺CD45RO⁺PD-1⁺ (G) cells out of the total peripheral lymphocytes from patients and healthy donors are shown. The P value was calculated using a Student’s t-test or Wilcoxon rank sum test.

PD-1 expression before and after the D2 gastrectomy

In this part, we detected the expression of PD-1 on the lymphocytes from blood samples drawn from postoperative patients. Blood samples were drawn on average of 27.24 d ± 5.06 d (range: 19-35 d) following surgery. A paired-t test was applied to compare the frequency of PD-1 on lymphocytes between the preoperative and operative blood samples. Strikingly, we found that surgery might be able to reduce the level of PD-1 expression on T cells. There was a significant decline in the PD-1 expression on lymphocytes from postoperative peripheral blood (22.37% ± 10.35% vs 16.00% ± 6.29%, P = 0.0001; Figure 2). A significant decrease was also observed for the level of PD-1 expression on CD4⁺ and CD8⁺ lymphocytes (7.10% ± 3.27% vs 5.26% ± 2.62%, P = 0.0008; 11.63% ± 7.06% vs 8.05% ± 3.60%, P = 0.001; Figure 2). The frequency of PD-1 expression on CD4⁺CD45RO⁺ and CD8⁺CD45RO⁺ lymphocytes from postoperative patients was also significantly lower than that derived from preoperative patients (5.16% ± 2.31% vs 3.67% ± 1.80%, P = 0.0085; 8.79% ± 5.15% vs 6.19% ± 3.20%, P < 0.0001; Figure 2). Similarly, the PD-1 expression on CD45RO⁺ lymphocytes was also significantly lower (13.94% ± 6.75% vs 9.86% ± 4.41%, P < 0.0001; Figure 2). Since the increase of PD-1 expression is dependent on antigen stimulation, one explanation for the observed results might be the lack of stimulation from tumor antigens following surgery.

Figure 2 Changes in programmed death 1 expression on all subsets before and after the D2 gastrectomy. A-F: The percentage of total programmed death 1⁺ (PD-1⁺) cells (A), CD4⁺PD-1⁺ (B), CD8⁺PD-1⁺ (C), CD45RO⁺PD-1⁺ (D), CD4⁺CD45RO⁺PD-1⁺ (E), and CD8⁺CD45RO⁺PD-1⁺ (F) cells of the peripheral lymphocytes derived from patients before and after the D2 gastrectomy are shown. The P value was calculated using an analysis of variance repeated-measures function.

PD-1 expression during chemotherapy

A total of 29 patients in the trial accepted an eight three-week cycles course of chemotherapy with oxaliplatin and capecitabine following a D2 gastrectomy. We drew peripheral blood samples on the day before the first cycle of chemotherapy (an average of 27.24 d ± 5.06 d after surgery), fourth cycle of chemotherapy (an average of 97.90 d ± 6.64 d after surgery) and the day after the eighth cycle of chemotherapy (an average of 171.14 d ± 8.73 d after surgery). There was a statistically significant decrease in PD-1 expression on the total lymphocytes (16.00% ± 6.29%, 13.62% ± 6.43% vs 13.33% ± 6.35%, P = 0.031; Figure 3) and CD8⁺T cells (8.05% ± 3.60%, 6.39% ± 3.59% vs 6.56% ± 3.64%, P = 0.009; Figure 3). A notably significant decline was also observed for the PD-1 expression on CD45RO⁺ lymphocytes (9.86% ± 4.41%, 6.48% ± 3.28% vs 7.71% ± 4.07%, P < 0.0001; Figure 3) and CD8⁺CD45RO⁺ lymphocytes (6.19% ± 3.20%, 3.86% ± 2.69% vs 4.44% ± 2.61%, P < 0.0001; Figure 3). However, the difference in PD-1 expression on CD4⁺ lymphocytes (5.26% ± 2.62%, 4.98% ± 2.40% vs 4.60% ± 2.15%, P = 0.276; Figure 3) and CD4⁺CD45RO⁺ lymphocytes (3.67% ± 1.80%, 3.23% ± 1.64% vs 3.27% ± 1.74%, P = 0.308; Figure 3) was not statistically significant.

Figure 3 Changes in programmed death 1 expression on all subsets during chemotherapy. A-F: The percentage of total programmed death 1⁺ (PD-1⁺) cells (A), CD4⁺PD-1⁺ (B), CD8⁺PD-1⁺ (C), CD45RO⁺PD-1⁺ (D), CD4⁺CD45RO⁺PD-1⁺ (E), and CD8⁺CD45RO⁺PD-1⁺ (F) cells of the peripheral lymphocytes derived from patients during chemotherapy are shown. The P value was calculated using an analysis of variance repeated-measures function.

Changes in theFoxP3⁺ Tregs in patients with gastric cancer

While analyzing the PD-1 expression on lymphocytes, we also detected the frequency of CD4⁺CD25⁺FoxP3⁺ T cells and CD4⁺CD45RO⁺FoxP3^high T cellsin the lymphocyte population (Figure 4A). The frequency of FoxP3⁺T cells and CD4⁺CD45RO⁺FoxP3^high T cellswas higher in the patients than in the healthy donors (1.76% ± 0.59% vs 0.87% ± 0.56%, P < 0.0001; 0.92% ± 0.45% vs 0.33% ± 0.27%, P < 0.0001; Figure 4B-G) and declined after the D2 gastrectomy was performed (1.76% ± 0.59% vs 1.26% ± 0.62%, P = 0.0004; 0.92% ± 0.45% vs 0.59% ± 0.40%, P = 0.0005; Figure 4B-G). Statistical difference was also observed in the frequency of CD4⁺CD45RO⁺FoxP3^high T cells in the peripheral lymphocytes during chemotherapy (0.59% ± 0.40%, 0.46% ± 0.29% vs0.37% ± 0.25%, P = 0.025; Figure 4B-G).

Figure 4 Treg and activated Treg cells in the peripheral blood of donors and patients. A: Scatter plots are shown from one representative patient. Relationships of the diagrams are denoted with arrows and gates; B-G: The percent of TCD4⁺CD25⁺FoxP3⁺ and CD4⁺CD45RO⁺FoxP3^high cells in the peripheral lymphocytes from the donors and patients during treatment were shown and the P value was calculated using an analysis of variance repeated-measures function.

Relativity between PD-1 expression and FoxP3⁺ Tregs

Previous research has suggested that PD-1⁺ T cells and Tregs arecorrelative in the tumor tissues and tumor-involved lymph nodes in both breast and papillary thyroid cancer[12,13]. However, no clear correlations between the frequency of PD-1 expression and the number of CD4⁺CD25⁺FoxP3⁺ T cellsobserved in the peripheral blood of preoperative patients (r = 0.4008, P < 0.0001; Figure 5) but significant correlation between CD4⁺CD45RO⁺FoxP3^high T cells and PD-1 expression (r = 0.5622, P < 0.0001; Figure 5) were observed in our study.

Figure 5 Relative programmed death 1 expression on lymphocytes and the percent of Treg and activated Treg cells. A and B: Programmed death 1 expression on lymphocytes and the percent of CD4⁺CD25⁺FoxP3⁺ (A) and CD4⁺CD45RO⁺FoxP3^high (B) cells in the peripheral blood. PD-1: Programmed death 1.

DISCUSSION

Studies have shown that the PD-1/PD-L1 pathway plays a critical role in promoting T cell exhaustion[14]. In many types of tumor tissues, overexpression of PD-L1 has been found, with a similar pattern of PD-1 overexpression observed on tumor-infiltrating lymphocytes[15,16].

Supported by T-helper cells, CD8⁺ T cells can be activated, leading to the destruction of tumor cells through the perforin/granzyme and Fas/Fas ligand (FasL) apoptosis pathways. However, tumor cells have been found to inhibit the function of CD4⁺ and CD8⁺ T cells by boosting PD-1 expression[17,18]. This scenario has been observed in the peripheral blood of various cancer types, such as non-small cell lung cancers, actinic cheilitis, oral squamous cell carcinoma, and head and neck cancer[19-22].

Our analysis unveiled a notable increase in PD-1 expression on CD45RO⁺ lymphocytes in gastric cancer. CD45RO is a surface antigen employed to differentiate memory T cells from naive T cells. When antigens are reintroduced, CD4⁺CD45RO⁺ T cells are seen to respond rapidly and robustly, migrating to the antigen source and aiding B cells in antibody production[23,24].

Several studies have suggested that CD8⁺CD45RO⁺ T cells serve as a more effective independent prognostic factor for metastatic colorectal cancer in Cox regression multivariate analysis compared to traditional markers like CEA and LDH[25-27]. Given this evidence, it seems likely that the upregulation of PD-1 on CD45RO⁺ T cells is a consequence of tumor cell stimulation, thereby facilitating tumor immune escape from memory T cells.

PD-1/PD-L1 expression can be induced or maintained by many cytokines, such as type I IFn and IFNγ. Research has shown that tumor-associated plasmacytoid DCs produce large amounts of type I IFn[28], which can in turn induce PD-1/PD-L1 expression[29]. The decline in these cytokines following tumor resection might be the underlying cause of the observed reduction in PD-1 expression.

Research conducted by Maeda et al[30] found that the populations of CD4⁺, CD8⁺ and NK cells in the peripheral blood of patients with metastatic colorectal cancer remained stable following FOLFOX administration, yet the number of regulatory cells exhibited a significant decline. A similar drop in the Tregs population was observed in patients treated with paclitaxel-based chemotherapy[31]. Data from our present study reveal a trend of significant decline or reduction in PD-1 expression and population of FoxP3⁺ Tregs in patients undergoing surgery and chemotherapy.

We observed that the population of regulatory T cells was higher in patients compared to donors, which is consistent with prior findings in prostate, lung, pancreatic, and breast cancer studies[32,33]. The increased population of Tregs in tumor-bearing patients could potentially arise from the secretion of TGF-β, IL-10, and H-ferritin, which have been known to induce CD4⁺CD25⁻ T cells to transition into CD4⁺CD25⁺ T cells and upregulate the expression of FoxP3[34-36].

Interestingly, this mechanism might also be responsible for the observed decrease in the number of peripheral Tregs following tumor tissue removal. Moreover, several studies have indicated that drugs like cyclophosphamide, fludarabine, and paclitaxel could down-regulate the quantity and function of Tregs in cancer patients[37,38].

These findings provide a theoretical foundation for the treatment of tumors with PD-1/PDL-1 blockers in combination with chemotherapy drugs, offering a potential strategy to optimize cancer immunotherapy.

In this study, CD4⁺CD45RO⁺FoxP3⁺ appears to have a stronger correlation to PD-1 expression than Tregs in peripheral blood. Previous detection of FoxP3 at both the mRNA and protein levels has shown that human CD25^highCD4⁺ T cells indeed express FoxP3[39,40], indicating that the population of CD4⁺CD45RO⁺FoxP3⁺ cells can serve as a reflection of CD25^highCD45RA^-FoxP3^high activated Treg cells (aTreg cells).

Moreover, the CD4⁺FoxP3⁺T cells in peripheral blood comprise three subpopulations, distinguished by differing levels of FoxP3 and cell surface molecules CD45RA and CD25. Notably, only CD25^highCD45RA^-FoxP3^high cells (aTregs) are terminally differentiated and exhibit high suppressive capacities[41].

CONCLUSION

The exploration of PD-1 expression impacts on immune subsets and the abundance of FoxP3⁺ Tregs in peripheral blood could provide invaluable insights for future research on the PD-1/PDL-1 axis, tumor recurrence, and tumor immune escape. Additionally, these findings may also serve as potential biomarkers for studies involving the timing and dosing of clinical anti-PD-1 antibodies.

ARTICLE HIGHLIGHTS

Research background

Programmed death 1 (PD-1) and CD4⁺CD25⁺FoxP3⁺ expression in peripheral blood T-cells have been identified in multiple cancer types, but their variation during surgery and chemotherapy in gastric cancer remains elusive. Understanding this could illuminate tumor recurrence mechanisms and guide optimal anti-PD-1 antibody treatment strategies.

Research motivation

Despite known PD-1 and CD4⁺CD25⁺FoxP3⁺ expression in various cancers, the specific changes during surgery and chemotherapy, and their relationship in gastric cancer, remain undefined. This study seeks to shed light on these variations, potentially offering insights into tumor recurrence, immune evasion, and the clinical application of anti-PD-1 antibodies in gastric cancer.

Research objectives

The study aims to observe and analyze the expression characteristics of peripheral lymphocyte PD-1 and FoxP3⁺ regulatory T cells (FoxP3⁺Tregs) in gastric cancer patients, both prior to and following surgery or chemotherapy, to better understand their roles and implications in gastric cancer treatment.

Research methods

In this study, 29 gastric cancer patients, post-D2 gastrectomy and undergoing chemotherapy, provided 10 mL peripheral blood samples during various perioperative phases. PD-1 expression was analyzed on specific lymphocyte subsets, with an additional 29 age-matched healthy donors serving as a control group.

Research results

The study found a significant elevation in PD-1 expression and FoxP3⁺ Tregs in gastric cancer patients, which decreased notably post-D2 gastrectomy. A positive correlation was identified between PD-1 expression and the number of activated FoxP3high Tregs in peripheral lymphocytes, especially during postoperative chemotherapy.

Research conclusions

Alterations in PD-1 expression and regulatory T cell activation during gastric cancer treatment could provide valuable insights for understanding tumor immune evasion. These findings may also influence the clinical application of anti-PD-1 antibodies in gastric cancer therapy.

Research perspectives

The changes observed in PD-1 expression and regulatory T cell activation during gastric cancer treatments pave the way for deeper exploration into tumor immune evasion mechanisms. These findings could also shape the future clinical application and optimization of anti-PD-1 antibodies in treating gastric cancer.