Reference - Detail
RRC ID | 82573 |
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Author | Fuchizawa H, Ando K, Motoi N, Iizuka T, Inoue M, Mitani K, Sano Y, Takenobu H, Haruta M, Onuki R, Matsuoka Y, Kamijo T, Kageyama Y. |
Title | STAT3 Contributes a Favorable Response to Pembrolizumab Through IFN-γ-induced Apoptosis in Urothelial Cancer. |
Journal | Anticancer Res |
Abstract |
BACKGROUND/AIM:Pembrolizumab, a second-line therapy for platinum-refractory advanced urothelial carcinoma (UC), is needed to improve objective response rate. Hence, it is crucial to identify optimal predictive biomarkers of responses. This study aimed to clarify the predictive value and role of signal transducer and activator of transcription 3 (STAT3) in selecting patients with advanced UC who might benefit clinically from pembrolizumab therapy. PATIENTS AND METHODS:We retrospectively analyzed 31 patients who received pembrolizumab therapy for UC. STAT3, phosphorylated STAT3 (p-STAT3), and PD-L1 expression were determined using tissue microarrays constructed from patient-derived specimens, and the association of these expression levels with overall survival was analyzed. We assessed the functional role of STAT3 in bladder cancer cell lines in response to interferon-gamma (IFN-γ). RESULTS:Patients with high STAT3 or p-STAT3 expression, and high platelet-to-lymphocyte ratio (PLR) (n=6) had a significantly shorter OS; in the other patients (n=25), high STAT3 or p-STAT3 expression was significantly associated with improved prognosis. IFN-γ-induced apoptosis was partially dependent on STAT3 in T24 cells but not in JMSU1 cells. CONCLUSION:In patients with advanced UC, STAT3 plays a key role in mediating the efficacy of pembrolizumab through apoptosis in response to IFN-γ. |
Volume | 44(5) |
Pages | 1925-1930 |
Published | 2024-5-1 |
DOI | 10.21873/anticanres.16994 |
PII | 44/5/1925 |
PMID | 38677727 |
MeSH | Antibodies, Monoclonal, Humanized* / pharmacology Antibodies, Monoclonal, Humanized* / therapeutic use Antineoplastic Agents, Immunological / pharmacology Antineoplastic Agents, Immunological / therapeutic use Apoptosis* / drug effects B7-H1 Antigen / metabolism Cell Line, Tumor Humans Interferon-gamma* / metabolism Interferon-gamma* / pharmacology Prognosis Retrospective Studies STAT3 Transcription Factor* / metabolism Urinary Bladder Neoplasms / drug therapy Urinary Bladder Neoplasms / metabolism Urinary Bladder Neoplasms / pathology Urologic Neoplasms / drug therapy Urologic Neoplasms / metabolism Urologic Neoplasms / pathology |
IF | 1.994 |
Resource | |
Human and Animal Cells | T24(RCB2536) JMSU1(RCB2227) |