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Article Open Access

Preoperative PD‑1+CD4+ lymphocytes reflect immunological and physical frailty and are associated with postoperative infectious complications following gastrectomy for gastric cancer

  • Authors:
    • Naoyuki Uehata
    • Hironori Tsujimoto
    • Nozomi Ito
    • Toru Kubo
    • Hiromi Miyazaki
    • Hiroyuki Horiguchi
    • Keita Kouzu
    • Seiichiro Fujishima
    • Takafumi Suzuki
    • Risa Kariya
    • Asuma Ide
    • Yoshihisa Yaguchi
    • Hideki Ueno
  • View Affiliations / Copyright

    Affiliations: Department of Surgery, National Defense Medical College, Tokorozawa, Saitama 359‑8513, Japan, Division of Biomedical Engineering, National Defense Medical College Research Institute, Tokorozawa, Saitama 359‑8513, Japan
    Copyright: © Uehata et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 575
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    Published online on: October 7, 2025
       https://doi.org/10.3892/ol.2025.15321
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Abstract

Postoperative infectious complications (PICs) are major adverse events following gastrectomy for gastric cancer. The present study investigated whether preoperative programmed cell death 1 (PD‑1)+CD4+ lymphocytes reflect immunological and physical frailty and predict PICs. A total of 85 patients who underwent gastrectomy for gastric cancer were retrospectively enrolled. Blood samples were collected preoperatively, and PD‑1+CD4+ cells were analyzed using flow cytometry. Patients were divided into PD‑1high (N=43) and PD‑1low (N=42) groups based on the median value of preoperative PD‑1+CD4+/CD4+ cells (cutoff, 22.3%). Preoperative immune‑inflammatory markers and nutritional indices included the neutrophil‑to‑lymphocyte ratio (NLR), platelet‑to‑lymphocyte ratio (PLR), C‑reactive protein‑to‑albumin ratio (CAR), prognostic nutrition index (PNI) and controlling nutritional status (CONUT) score. Physical vulnerability was assessed using the fall risk assessment score (FRAS) and Charlson comorbidity index (CCI). The PD‑1high group was older than the PD‑1low group, with no significant differences in sex, comorbidities, or surgical and pathological factors. The PD‑1high group had a significantly higher incidence of the PICs (42 vs. 19%; P<0.05). In addition, the PD‑1high group exhibited higher C‑reactive protein levels, and lower total lymphocyte counts and albumin levels compared with the PD‑1low group (P<0.05, respectively). The two groups had significant differences in preoperative NLR, CAR, PNI, CONUT score and FRAS. Notably, there were significant associations between PD‑1+CD4+/CD4+ cells and NLR, PLR, CONUT score, PNI, FRAS and CCI (all P<0.05). Preoperative PD‑1+CD4+/CD4+ cells were significantly associated with increased PIC risk and markers of immunological and physical frailty. This biomarker may be useful for identifying vulnerable patients requiring tailored perioperative care.
View Figures

Figure 1

Gating strategy for flow cytometric
analysis. Blood samples were labeled with fluorescent
dye-conjugated monoclonal antibodies against PD-1-PE, CD4-PC7 and
CD3-FITC. PD-1+CD4+ cells were defined as
PD-1 positive cells (square) with double positive CD3 and CD4 cells
(circle). PD-1, programmed cell death 1.

Figure 2

Correlation between
PD-1+CD4+/CD4+ cells and
immune-inflammatory markers and nutritional indices. (A) There are
significant positive correlations between
PD-1+CD4+/CD4+ cells and NLR, (C)
PLR and (D) CONUT score (P<0.05), (E) whereas a significant
negative correlation is observed between
PD-1+CD4+/CD4+ cells and PNI
(P<0.05). (B) There is no correlation between
PD-1+CD4+/CD4+ cells and CAR
(P=0.23). The gray zone indicates the 95% confidence interval. The
regression equations are inserted. NLR, neutrophil-to-lymphocyte
ratio; CAR, C-reactive protein-to-albumin ratio; PLR,
platelet-to-lymphocyte ratio; CONUT, controlling nutrition status;
PNI, prognostic nutritional index; PD-1, programmed cell
death-1.

Figure 3

Correlation between the
PD-1+CD4+/CD4+ cells and physical
status. (A) The PD-1+CD4+/CD4+
cells are significantly increased as the ASA-PS increases
(P<0.05). (B) There are significant positive correlations
between PD-1+CD4+/CD4+ cells, age
(P<0.01), (C) the fall risk assessment score (P<0.05) and (D)
the Charlson comorbidity index (P<0.01). The gray zone indicates
the 95% confidence interval. The regression equations are inserted.
ASA-PS, American Society of Anesthesiologists physical status;
FRAS, fall risk assessment score; CCI, Charlson comorbidity index;
PD-1, programmed cell death-1.
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Copy and paste a formatted citation
Spandidos Publications style
Uehata N, Tsujimoto H, Ito N, Kubo T, Miyazaki H, Horiguchi H, Kouzu K, Fujishima S, Suzuki T, Kariya R, Kariya R, et al: Preoperative PD‑1<sup>+</sup>CD4<sup>+</sup> lymphocytes reflect immunological and physical frailty and are associated with postoperative infectious complications following gastrectomy for gastric cancer. Oncol Lett 30: 575, 2025.
APA
Uehata, N., Tsujimoto, H., Ito, N., Kubo, T., Miyazaki, H., Horiguchi, H. ... Ueno, H. (2025). Preoperative PD‑1<sup>+</sup>CD4<sup>+</sup> lymphocytes reflect immunological and physical frailty and are associated with postoperative infectious complications following gastrectomy for gastric cancer. Oncology Letters, 30, 575. https://doi.org/10.3892/ol.2025.15321
MLA
Uehata, N., Tsujimoto, H., Ito, N., Kubo, T., Miyazaki, H., Horiguchi, H., Kouzu, K., Fujishima, S., Suzuki, T., Kariya, R., Ide, A., Yaguchi, Y., Ueno, H."Preoperative PD‑1<sup>+</sup>CD4<sup>+</sup> lymphocytes reflect immunological and physical frailty and are associated with postoperative infectious complications following gastrectomy for gastric cancer". Oncology Letters 30.6 (2025): 575.
Chicago
Uehata, N., Tsujimoto, H., Ito, N., Kubo, T., Miyazaki, H., Horiguchi, H., Kouzu, K., Fujishima, S., Suzuki, T., Kariya, R., Ide, A., Yaguchi, Y., Ueno, H."Preoperative PD‑1<sup>+</sup>CD4<sup>+</sup> lymphocytes reflect immunological and physical frailty and are associated with postoperative infectious complications following gastrectomy for gastric cancer". Oncology Letters 30, no. 6 (2025): 575. https://doi.org/10.3892/ol.2025.15321
Copy and paste a formatted citation
x
Spandidos Publications style
Uehata N, Tsujimoto H, Ito N, Kubo T, Miyazaki H, Horiguchi H, Kouzu K, Fujishima S, Suzuki T, Kariya R, Kariya R, et al: Preoperative PD‑1<sup>+</sup>CD4<sup>+</sup> lymphocytes reflect immunological and physical frailty and are associated with postoperative infectious complications following gastrectomy for gastric cancer. Oncol Lett 30: 575, 2025.
APA
Uehata, N., Tsujimoto, H., Ito, N., Kubo, T., Miyazaki, H., Horiguchi, H. ... Ueno, H. (2025). Preoperative PD‑1<sup>+</sup>CD4<sup>+</sup> lymphocytes reflect immunological and physical frailty and are associated with postoperative infectious complications following gastrectomy for gastric cancer. Oncology Letters, 30, 575. https://doi.org/10.3892/ol.2025.15321
MLA
Uehata, N., Tsujimoto, H., Ito, N., Kubo, T., Miyazaki, H., Horiguchi, H., Kouzu, K., Fujishima, S., Suzuki, T., Kariya, R., Ide, A., Yaguchi, Y., Ueno, H."Preoperative PD‑1<sup>+</sup>CD4<sup>+</sup> lymphocytes reflect immunological and physical frailty and are associated with postoperative infectious complications following gastrectomy for gastric cancer". Oncology Letters 30.6 (2025): 575.
Chicago
Uehata, N., Tsujimoto, H., Ito, N., Kubo, T., Miyazaki, H., Horiguchi, H., Kouzu, K., Fujishima, S., Suzuki, T., Kariya, R., Ide, A., Yaguchi, Y., Ueno, H."Preoperative PD‑1<sup>+</sup>CD4<sup>+</sup> lymphocytes reflect immunological and physical frailty and are associated with postoperative infectious complications following gastrectomy for gastric cancer". Oncology Letters 30, no. 6 (2025): 575. https://doi.org/10.3892/ol.2025.15321
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