{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T10:15:01Z","timestamp":1780049701239,"version":"3.53.1"},"reference-count":26,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology CR"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The prognostic value of the International Association for the Study of Lung Cancer (IASLC) grading system in anaplastic lymphoma kinase (ALK)\u2010positive invasive non\u2010mucinous adenocarcinoma (INMA) remains unclear, particularly in relation to the tumor immune microenvironment (TIME). This retrospective study included 108 patients with ALK\u2010positive INMA. Tumors were graded according to the IASLC system. Clinicopathological features, progression\u2010free survival (PFS), and overall survival (OS) were analyzed. Immunohistochemistry was used to assess PD\u2010L1 expression and tumor\u2010infiltrating lymphocytes (TILs), including CD4+, CD8+, and FoxP3+ regulatory T cells. Associations were evaluated using Kaplan\u2013Meier analysis, Cox regression models, and correlation analyses. Higher IASLC grades were significantly associated with more aggressive pathological features, elevated PD\u2010L1 expression, and shorter progression\u2010free survival (PFS). Higher\u2010grade tumors exhibited enhanced T\u2010cell infiltration, predominantly driven by CD8+ T cells, while no significant difference in FoxP3+ Treg density was observed across grades. Notably, the CD4:CD8 ratio decreased, whereas the CD8:FoxP3 ratio increased with tumor grade, indicating a shift toward a CD8\u2010dominant immune microenvironment. Importantly, this cytotoxic predominance occurred in parallel with elevated PD\u2010L1 expression, suggesting an immune context consistent with adaptive immune resistance rather than effective anti\u2010tumor immunity. The IASLC grading system effectively identifies a high\u2010risk subgroup of ALK\u2010positive INMA characterized by aggressive tumor behavior and a dynamically regulated immune microenvironment. High\u2010grade tumors exhibit features of immune engagement coupled with checkpoint\u2010mediated regulation, supporting a model of adaptive immune resistance. These findings underscore the necessity of combination therapeutic strategies that simultaneously target ALK and immune checkpoint modulation in high\u2010grade INMA.<\/jats:p>","DOI":"10.1002\/2056-4538.70093","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T11:29:42Z","timestamp":1778585382000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The prognostic significance of the\n                    <scp>IASLC<\/scp>\n                    grading system in\n                    <scp>ALK<\/scp>\n                    \u2010positive invasive non\u2010mucinous adenocarcinoma of the lung: correlation with clinicopathological features"],"prefix":"10.1002","volume":"12","author":[{"given":"Dongmei","family":"Gu","sequence":"first","affiliation":[{"name":"Department of Pathology The First Affiliated Hospital of Soochow University  Suzhou 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