{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T13:09:57Z","timestamp":1789564197943,"version":"build-2803163510"},"reference-count":31,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Reports"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Programmed death\u2010ligand 1 (PD\u2010L1) expression is widely used to guide immune checkpoint inhibitor (ICI) therapy in advanced nonsmall cell lung cancer (NSCLC); however, substantial heterogeneity in clinical outcomes persists among patients with high PD\u2010L1 expression. Reliable biomarkers for further stratifying this population are still lacking. This study investigated whether genomic alterations and features of the tumor immune microenvironment could explain this variability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a retrospective single\u2010center study including 91 patients with advanced NSCLC and PD\u2010L1 tumor proportion score (TPS) \u2265\u200950% who received ICI\u2010based therapy. Clinical outcomes were assessed according to PD\u2010L1 expression levels, genomic profiles, and tumor immune microenvironment characteristics. Tumor\u2010infiltrating lymphocytes (TILs) and tertiary lymphoid structures (TLSs) were evaluated in available tumor specimens from 75 patients. Multiplex immunohistochemistry (mIHC) was performed in a subset of 30 patients to characterize the immune cellular composition underlying TIL\u2010based stratification. Kaplan\u2013Meier survival analysis and multivariable Cox regression were used to identify factors associated with progression\u2010free survival (PFS) and overall survival (OS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      At a median follow\u2010up of 19.1\u2009months, the objective response rate was 31.9%, the median PFS was 10.7\u2009months, and the median OS was 43.5\u2009months. No significant survival differences were observed between the TPS 50%\u201389% and TPS\u2009\u2265\u200990% subgroups. TP53 mutation was associated with shorter PFS and remained an independent adverse prognostic factor. In contrast, high TIL infiltration was independently associated with improved PFS and OS, and this OS benefit was most pronounced in the TPS\u2009\u2265\u200990% subgroup. mIHC analysis revealed that high\u2010TIL tumors exhibited increased stromal CD8\n                      <jats:sup>+<\/jats:sup>\n                      T\u2010cell infiltration, enriched NK\u2010cell populations, and a more proinflammatory macrophage profile, providing biological support for TIL\u2010based stratification. TLS presence was not significantly associated with survival outcomes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>PD\u2010L1 expression alone does not fully account for the outcome heterogeneity observed in PD\u2010L1\u2010high NSCLC treated with ICIs. Integrating genomic alterations\u2014particularly TP53 mutation status\u2014with tumor immune microenvironment features, such as TIL density, may help refine prognostic stratification in this population.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cnr2.70648","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T03:05:18Z","timestamp":1786676718000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>TP53<\/scp>\n                    Mutation and Tumor\u2010Infiltrating Lymphocytes as Predictors of\n                    <scp>PD<\/scp>\n                    \u20101\/\n                    <scp>PD<\/scp>\n                    \u2010\n                    <scp>L1<\/scp>\n                    Inhibitor Efficacy in\n                    <scp>PD<\/scp>\n                    \u2010\n                    <scp>L1<\/scp>\n                    \u2010High Advanced\n                    <scp>NSCLC<\/scp>"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-5966-8484","authenticated-orcid":false,"given":"Hui","family":"Yan","sequence":"first","affiliation":[{"name":"Department of Oncology The First Affiliated Hospital of Soochow University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Oncology The First Affiliated Hospital of Soochow University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yushuang","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Pathology The First Affiliated Hospital of Soochow University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Oncology The First Affiliated Hospital of Soochow University  Suzhou 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