{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T21:32:49Z","timestamp":1789853569102,"version":"4.0.1"},"reference-count":44,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T00:00:00Z","timestamp":1770681600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T00:00:00Z","timestamp":1770681600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["W81XWH\u201022\u20101\u20100913"],"award-info":[{"award-number":["W81XWH\u201022\u20101\u20100913"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Smoking is a modifiable risk factor for prostate cancer (PCa) diagnosis, recurrence, and mortality. While the mutagenic effects of tobacco are well\u2010documented, the immunological consequences of smoking within the tumor microenvironment (TME) are poorly understood. This study investigates how smoking reshapes the PCa immune landscape and how the associated changes could potentially be associated with patient survival.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Tumor tissues from smoker and nonsmoker prostate cancer patients were subjected to multiplex gene expression analysis of immune cell types using the nanoString nCounter\u00ae PanCancer immune profiling panel to examine the effect of smoking behavior on the immune landscape. Gene expression data were also analyzed using Enrichr to identify differentially activated pathways in smoker versus nonsmoker patients. Further, we surveyed public databases to examine the association between top differentially\u2010expressed genes and altered immune cell abundance with patient survival.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Current\u2010smokers exhibited significantly higher infiltration of tumor\u2010associated macrophages (TAMs) (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.036) and regulatory T cells (Tregs) (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.045), compared to nonsmokers, with a trend for lower mast cell infiltration (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.055). A significant positive correlation (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.42;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.036) was observed between TAMs with Tregs in all samples, with a stronger correlation in current\u2010smokers (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.88;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.008) than nonsmokers (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.26;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.403). A total of 89 DEGs were identified between current\u2010smokers and nonsmokers, associated with upregulation of immunosuppressive pathways including \u201cprimary immunodeficiency\u201d and \u201cPD\u2010L1 expression and PD\u20101 checkpoint,\u201d and downregulation of \u201cantigen\u2010processing and \u2010presentation\u201d and \u201cNF\u2010kappa\u2010B signaling\u201d pathways. Key upregulated genes, MAGEA3, POU2AF1, and SEMG1, correlated with immune suppression markers and poorer PCa patient survival. Concomitant high TAM and Treg infiltration also significantly correlated with reduced overall survival (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.04). No significant differences were observed between current\u2010smokers and former\u2010smokers, who exhibited patterns similar to nonsmokers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings suggest that active smoking creates an immunosuppressive TME, potentially facilitating rapid tumor growth and aggressive progression. Smoking cessation may reverse these changes, highlighting the clinical significance of smoking behavior in disease outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pros.70142","type":"journal-article","created":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T10:21:58Z","timestamp":1770718918000},"page":"753-762","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Smoking Behavior Is Associated With an Altered Immune Landscape in Prostate Cancer: Implications for Patient Outcomes"],"prefix":"10.1002","volume":"86","author":[{"given":"Amod","family":"Sharma","sequence":"first","affiliation":[{"name":"Department of Cell and Molecular Biology University of Mississippi Medical Center Jackson Mississippi USA"},{"name":"Cancer Center and Research Institute University of Mississippi Medical Center Jackson Mississippi 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