{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T22:07:47Z","timestamp":1777759667611,"version":"3.51.4"},"reference-count":74,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T00:00:00Z","timestamp":1777161600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Peripheral T-cell lymphomas (PTCLs) are malignancies of mature T cells with a poor prognosis. Most PTCL cases express follicular T-helper (TFH) cell antigens and are classified as TFH cell lymphoma (TFHL). Contact-dependent signaling between CD40 and its ligand, CD154, is essential for immune functions. CD154 is expressed by activated T cells, while CD40 is found on B cells, follicular and other dendritic cells, macrophages, and stromal cells. Although the CD40\u2013CD154 crosstalk is a key costimulatory pathway in immune responses, data on its role in PTCLs are limited. To explore the role of the CD40\u2013CD154 axis in TFHLs, we conducted an in-depth immunomorphological study of 111 PTCL cases, including 93 TFHL cases. We found that neoplastic T cells in TFHL are consistently CD154-positive. The CD154 expression increased in histologically advanced cases and correlated with the extent of CD40 positivity. We showed that CD154-positive neoplastic T cells recapitulate the intranodal migration of normal TFH cells, disrupting and remodeling each functional compartment, thereby explaining the disease-related immune dysfunction. Our findings indicate that pathological CD40\u2013CD154 interaction is a potential driver mechanism in TFHL and offers a promising target for future therapies.<\/jats:p>","DOI":"10.3390\/cells15090785","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T13:32:22Z","timestamp":1777469542000},"page":"785","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Immunomorphological Analysis of the CD40\u2013CD154 Interaction in T Follicular Helper Cell Lymphoma Emphasizes the Significance of the CD40\u2013CD154 Axis in the Disease"],"prefix":"10.3390","volume":"15","author":[{"given":"D\u00f3ra M\u00e1ria","family":"Janotka","sequence":"first","affiliation":[{"name":"Laboratory of Tumor Pathology and Molecular Diagnostics, 6726 Szeged, Hungary"},{"name":"Pathology Department, Semmelweis Hospital, 6400 Kiskunhalas, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zita","family":"Borb\u00e9nyi","sequence":"additional","affiliation":[{"name":"Department of Hematology, Internal Medicine Clinic South Division, Albert Szent-Gy\u00f6rgyi Clinical Center, University of Szeged, 6725 Szeged, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kl\u00e1ra","family":"Piukovics","sequence":"additional","affiliation":[{"name":"Department of Hematology, Internal Medicine Clinic South Division, Albert Szent-Gy\u00f6rgyi Clinical Center, University of Szeged, 6725 Szeged, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M\u00e1ty\u00e1s","family":"Bukva","sequence":"additional","affiliation":[{"name":"Department of Immunology, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, 6725 Szeged, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annam\u00e1ria","family":"Bakos","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Albert Szent-Gy\u00f6rgyi Clinical Center, University of Szeged, 6725 Szeged, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enik\u0151","family":"Bagdi","sequence":"additional","affiliation":[{"name":"Laboratory of Tumor Pathology and Molecular Diagnostics, 6726 Szeged, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L\u00e1szl\u00f3","family":"Kren\u00e1cs","sequence":"additional","affiliation":[{"name":"Laboratory of Tumor Pathology and Molecular Diagnostics, 6726 Szeged, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1046\/j.1365-2141.2003.04335.x","article-title":"Angioimmunoblastic T-cell lymphoma","volume":"121","author":"Dogan","year":"2003","journal-title":"Br. 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