{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:04:04Z","timestamp":1785423844161,"version":"3.56.0"},"reference-count":59,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81970867"],"award-info":[{"award-number":["81970867"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82101204"],"award-info":[{"award-number":["82101204"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Respiratory Research Project of National Clinical Research Center for Respiratory Diseases","award":["HXZX-20210201"],"award-info":[{"award-number":["HXZX-20210201"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2026,6,23]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Juvenile-onset recurrent respiratory papillomatosis (JORRP) is a rare, human papillomavirus (HPV)-driven pediatric disease characterized by recurring papillomas in the respiratory tract. The contribution of dysregulated T-cell immunity to disease severity remains poorly understood. This study included 97 JORRP patients and 124 controls. Due to sample limitations, downstream analyses, including flow cytometry, TCR, and RNA sequencing, were performed on distinct patient subsets (detailed in Methods). We identified a selective expansion of TCR V\u03b23\n                      <jats:sup>+<\/jats:sup>\n                      T cells, including expanded TRBV28 clonotypes, in patients with aggressive disease. These T cells exhibited heightened cytotoxicity and activation markers, and were enriched in papilloma tissues. Within the tumor microenvironment, gene expression profiling revealed upregulated chemokine signaling pathways (CCR2\/CCL7, CXCR6\/CXCL16) and key immunosuppressive markers, including PD-L1 and TGF-\u03b21. Our findings demonstrate a tumor-specific clonal expansion and functional alteration of TCR V\u03b23\n                      <jats:sup>+<\/jats:sup>\n                      T cells in JORRP, suggesting these pathways as preliminary targets for further investigation.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        Our study identifies a disease-specific T-cell signature in juvenile-onset recurrent respiratory papillomatosis (JORRP), marked by the clonal expansion of TCR V\u03b23\n                        <jats:sup>+<\/jats:sup>\n                        T cells with distinct TRBV28-dominant clonotypes. These T cells exhibit heightened cytotoxic potential and activation markers but appear functionally constrained within an immunosuppressive tumor microenvironment. Additionally, we discovered a dysregulated chemokine axis (CCR2\/CCL7 and CXCR6\/CXCL16), which likely facilitates T-cell recruitment, yet fails to sustain their antiviral activity. These findings provide mechanistic insights into why HPV-driven papillomas persist despite immune infiltration. Importantly, our work suggests that targeting TCR V\u03b23\n                        <jats:sup>+<\/jats:sup>\n                        T-cell responses and modulating key chemokine pathways could offer novel immunotherapeutic strategies to restore immune control and reduce disease recurrence in JORRP patients.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.01080-25","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T13:29:26Z","timestamp":1780406966000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Clonal expansion and phenotypic alterations of TCR V\u03b23\n                    <sup>+<\/sup>\n                    T cells in juvenile-onset recurrent respiratory papillomatosis: implications for tumor-associated immunity and chemokine-mediated T-cell trafficking"],"prefix":"10.1128","volume":"100","author":[{"given":"Shilan","family":"Li","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/013xs5b60","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Otorhinolaryngology Head and Neck Surgery, National Center for Children\u2019s Health, Beijing Children\u2019s Hospital, Capital Medical University","place":["Beijing, China"]},{"id":[{"id":"https:\/\/ror.org\/013q1eq08","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Otorhinolaryngology, Eye Ear Nose and Throat Hospital of Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1257-3079","authenticated-orcid":false,"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/013xs5b60","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratory of Tumor Immunology, National Center for Children\u2019s Health, 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