{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T05:07:34Z","timestamp":1789103254761,"version":"build-2803163510"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"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>\n                      Purpose of the study was to investigate the prognostic impact of HLA-G expression in patients with cervical squamous cell carcinoma (CSCC), and to further analyze its correlations with PD-L1 and CD8-positive (CD8\n                      <jats:sup>+<\/jats:sup>\n                      ) tumor-infiltrating lymphocytes (TILs) within the tumor microenvironment (TME).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A total of 139 formalin-fixed paraffin-embedded (FFPE) tissue samples were collected from patients diagnosed with CSCC. Immunohistochemistry (IHC) and multiplex immunofluorescence (mIF) staining were performed to assess the expression of immune biomarkers, including HLA-G, its receptor ILT2, PD-L1, total TILs and CD8\n                      <jats:sup>+<\/jats:sup>\n                      TILs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The overall positive expression rates were 86.8% for HLA-G, 85.1% for sHLA-G, 50.0% for PD-L1, and 70.2% for cases with low TIL infiltration in the TME. These immune biomarkers displayed distinct immunoreactivity patterns with remarkable intratumoral and stromal heterogeneity. ILT2 expression was positively correlated with CD8\n                      <jats:sup>+<\/jats:sup>\n                      TIL infiltration in both intratumoral and stromal compartments, yet rare cellular co-localization between ILT2 and CD8 was detected. Within tumoral regions, a strong positive correlation was identified between HLA-G and PD-L1 expression, and the two proteins were confirmed to be co-localized at the single-cell level in SCC lesions. Using the median HLA-G expression level of 61.0% as the cutoff value, patients with HLA-G expression above this threshold showed significantly worse overall survival (OS). The subgroup with high HLA-G\/sHLA-G and low TIL infiltration showed the worst prognosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The present study confirms that elevated HLA-G\/sHLA-G expression serves as an independent adverse prognostic factor for cervical cancer. Combined assessment of HLA-G, PD-L1 and TIL infiltration may enable risk-stratified prognostic management for patients with cervical cancer.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1957106","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T04:32:50Z","timestamp":1789101170000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Prognostic impact of HLA-G expression in cervical squamous cell carcinoma: correlation with PD-L1 and CD8-positive tumor infiltrating lymphocytes"],"prefix":"10.3389","volume":"17","author":[{"given":"Yi-Xiao","family":"Pan","sequence":"first","affiliation":[{"name":"Department of Public Research Platform, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University","place":["Linhai, Zhejiang, 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