{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T06:49:26Z","timestamp":1765349366922,"version":"3.46.0"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T00:00:00Z","timestamp":1765324800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Although standard chemotherapy combined with immunotherapy represented by programmed cell death -1(PD-1) blockade shows promise as a treatment approach for gastric cancer (GC), the drug response rates remain low. Identifying reliable biomarkers to predict patient response is urgently needed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We collected baseline (before receiving PD-1 inhibitors) peripheral blood samples from advanced GC patients (n=54) who underwent PD-1 inhibitors and platinum drugs from January 2022 to December 2023 and investigated PD-1 expression on effector memory T (TEM) between responders and non-responders according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) guidelines by low-dose computed tomography scan evaluation. Univariate and multivariate analyses were applied to identify potential predictive biomarker for chemo-immunotherapy combinations outcomes.\n                      <jats:italic>In vitro<\/jats:italic>\n                      cytotoxicity and cytokine detection were used to demonstrate the effects of PD-1 blockade on TEM cells with different levels of PD-1 expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The optimal cutoff values for percentages of PD-1\n                      <jats:sup>+<\/jats:sup>\n                      cells in TEM were 8.66%. Among advanced GC patients receiving anti-PD-1 therapy, responders exhibited a higher mean percentage of PD-1\n                      <jats:sup>+<\/jats:sup>\n                      cells in TEM (\n                      <jats:italic>P<\/jats:italic>\n                      = 0.017) than non-responders, which were associated with longer PFS. Univariate and multivariate Cox regression analyses demonstrated that higher percentage of PD-1\n                      <jats:sup>+<\/jats:sup>\n                      cells in TEM (HR = 0.191, 95% CI 0.065\u20130.560,\n                      <jats:italic>P<\/jats:italic>\n                      = 0.003) was independent protective factor in advanced GC patients receiving chemo-immunotherapy.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , PD-1 blockade enhanced TEM activation, as evidenced by increased cytotoxicity and IFN-\u03b3 secretion, leading to improved anti-tumor capacity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our data identify a high pretreatment percentage of PD-1\n                      <jats:sup>+<\/jats:sup>\n                      cells in TEM as a potential predictive biomarker for response to PD-1 blockade.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1720724","type":"journal-article","created":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T06:48:00Z","timestamp":1765349280000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Circulating PD-1+ effector memory T cells predict anti-PD-1 efficacy in advanced gastric 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