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. 2015 Mar;58(1):39-44.
Epub 2015 Mar 27.

Upregulation of Immune Checkpoint Molecules, PD-1 and LAG-3, on CD4+ and CD8+ T Cells after Gastric Cancer Surgery

Seigo Takaya  1 , Hiroaki Saito  1 , Masahide Ikeguchi  1
Affiliations

Upregulation of Immune Checkpoint Molecules, PD-1 and LAG-3, on CD4+ and CD8+ T Cells after Gastric Cancer Surgery

Seigo Takaya et al. Yonago Acta Med. 2015 Mar.

Abstract

Background: Surgery has been reported to suppress cell-mediated immunity; however, the detailed mechanisms responsible for this remain unclear. This study determined the expression of lymphocyte activation gene 3 (LAG-3) and programmed cell death 1 (PD-1) in lymphocytes following surgery for gastric cancer.

Methods: LAG-3 and PD-1 expression on both CD4+ and CD8+ T cells obtained pre- and post-operatively from gastric cancer patients were evaluated by multicolor flow cytometry.

Results: The total lymphocyte count decreased rapidly from preoperative levels, reaching a minimum on postoperative day 1 and remaining significantly decreased on days 3 and 7. PD-1(+)CD4(+) T cells significantly increased, reaching a maximum on postoperative day 1 and remaining significantly elevated on day 3. PD-1(+)CD8(+) T cells significantly increased and reached a maximum on day 7 before returning to the preoperative level on day 30. There were no statistically significant differences in the frequency of LAG-3(+)CD4(+) or LAG-3(+)CD8(+) T cells after surgery. There were significant positive correlations between PD-1 and LAG-3 expression on both CD4(+) andCD8(+) T cells.

Conclusion: PD-1 and LAG-3 expression on both CD4(+) and CD8(+) T cells was up-regulated and might be related to impaired cell-mediated immunity after surgery for gastric cancer.

Keywords: T-cell; gastric cancer; lymphocyte activation gene 3; programmed cell death 1.

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Figures

Fig. 1.
Fig. 1.
Changes in total leukocyte count (a), serum concentration of C-reactive protein (CRP) (b) and total lymphocyte count (c) after surgery. POD, postoperative day; Pre-op, preoperation.
Fig. 2.
Fig. 2.
(a) The reaction of isotypic control to CD4+ T cells after surgery by FACS. (b) Representative results for PD-1 on CD4+ T cells in peripheral blood obtained from gastric cancer patients after surgery by FACS. (c) Changes in PD-1 expression on CD4+ T cells after surgery. POD, postoperative day; Pre-op, preoperation.
Fig. 3.
Fig. 3.
(a) The reaction of isotypic control to CD4+ T cells after surgery by FACS. (b) Representative results for LAG-3 on CD4+ T cells in peripheral blood obtained from gastric cancer patients after surgery by FACS. (c) Changes in LAG-3 expression on CD4+ T cells after surgery. POD, postoperative day; Pre-op, preoperation.
Fig. 4.
Fig. 4.
(a) The reaction of isotypic control to CD8+ T cells after surgery by FACS. (b) Representative results for PD-1 on CD8+ T cells in peripheral blood obtained from gastric cancer patients after surgery by FACS. (c) Changes in PD-1 expression on CD8+ T cells after surgery. POD, postoperative day; Pre-op, preoperation.
Fig. 5.
Fig. 5.
(a) The reaction of isotypic control to CD8+ T cells after surgery by FACS. (b) Representative results for LAG-3 on CD8+ T cells in peripheral blood obtained from gastric cancer patients after surgery by FACS. (c) Changes in LAG-3 expression on CD8+ T cells after surgery. POD, postoperative day; Pre-op, preoperation.
Fig. 6.
Fig. 6.
Correlation between PD-1 and LAG-3 expression on CD4+ (a) and CD8+ T cells (b).
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