{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T14:56:15Z","timestamp":1782917775681,"version":"3.54.5"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"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>Immunotherapy research, particularly in the neoadjuvant setting, has largely focused on tumor-intrinsic determinants, with limited attention to host-related factors. Emotional distress (ED), a prevalent condition in cancer patients, remains poorly understood in the context of neoadjuvant immunotherapy (NAIT).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed a cohort of 68 patients with locally advanced OSCC treated with NAIT. ED was assessed using the EORTC QLQ-C30 to stratify patients, and clinical outcomes were evaluated to determine therapeutic efficacy. Serum neuroendocrine markers were measured to assess neuroendocrine activation. Integrated single-cell, spatial, and multiplexed imaging approaches were employed to characterize immune remodeling and macrophage-Treg interactions. A chronic restraint stress mouse model was established to investigate stress-associated tumor immune remodeling and therapeutic response during anti-PD-1 therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Elevated ED was associated with a lower disease control rate and inferior event-free survival. High-distress patients exhibited increased serum cortisol levels, which were associated with less favorable treatment outcomes. Multi-omics analyses suggested an immunosuppressive tumor microenvironment in distressed patients, characterized by regulatory T cell enrichment and increased macrophage\u2013Treg spatial association within organized niches.\n                      <jats:italic>In vivo<\/jats:italic>\n                      , RU486 treatment was associated with reduced tumor burden, improved survival, and partial modulation of immunosuppressive remodeling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Emotional distress may represent a clinically relevant and potentially modifiable host-related factor associated with NAIT outcomes in OSCC. Stress-associated glucocorticoid signaling may contribute to immunosuppressive tumor remodeling and less favorable therapeutic response. These findings provide a rationale for integrating psychosocial assessment and neuroendocrine-targeted interventions into perioperative immunotherapy strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1861003","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T14:27:07Z","timestamp":1782916027000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Emotional distress is associated with neuroendocrine-immune remodeling and less favorable neoadjuvant immunotherapy outcomes in oral squamous cell carcinoma"],"prefix":"10.3389","volume":"17","author":[{"given":"Ze-Chen","family":"Zhao","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan 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