Neoadjuvant Immunotherapy of Oral Squamous Cell Carcinoma Modulates Intratumoral CD4/CD8 Ratio and Tumor Microenvironment: A Multicenter Phase II Clinical Trial
| Autor: | Norbert Velich, Miklós Kásler, Csaba Forster-Horváth, Béla Zemplén, Eyal Talor, Paul Chretien, Gábor Répássy, Maria Godeny, Zsuzsa Suba, György Szabó, Andrea Ladányi, Károly Pócza, József Tímár, Júlia Lukits, Éva Remenár, Zsuzsa Balatoni, János Elo, Beáta Bencsik, Balazs Dome |
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| Rok vydání: | 2005 |
| Předmět: |
Adult
Male Cancer Research medicine.medical_specialty Pathology Maximum Tolerated Dose Cyclophosphamide medicine.medical_treatment Indomethacin CD4-CD8 Ratio H&E stain Injections Intralesional Gastroenterology Drug Administration Schedule Internal medicine Carcinoma Humans Medicine Grading (tumors) Survival rate Neoadjuvant therapy Aged Neoplasm Staging Aged 80 and over Dose-Response Relationship Drug business.industry Biopsy Needle Cancer Middle Aged medicine.disease Immunohistochemistry Neoadjuvant Therapy Survival Rate Regimen Treatment Outcome Oncology Carcinoma Squamous Cell Interleukin-2 Drug Therapy Combination Female Mouth Neoplasms Immunotherapy business Follow-Up Studies medicine.drug |
| Zdroj: | Journal of Clinical Oncology. 23:3421-3432 |
| ISSN: | 1527-7755 0732-183X |
| Popis: | Purpose To investigate the clinicopathologic effects of local neoadjuvant Leukocyte Interleukin Injection (LI) regimen in oral squamous cell carcinoma (OSCC) patients. Treatment regimen included LI 800 IU/d as interleukin-2 (IL-2), administered half peritumorally and half perilymphatically five times per week for 3 weeks; low-dose cyclophosphamide; indomethacin; zinc; and multivitamins. Patients and Methods Thirty-nine patients diagnosed with T2-3N0-2M0 OSCC participated in the pathology portion of this phase II multicenter study (19 LI-treated patients and 20 historical controls). Clinical responses were determined by imaging. Paraffin-embedded tumor samples were obtained at surgery for all patients. Surgery for the LI-treated group was performed between days 14 and 54 after the end of treatment. Histologic evaluation, pathologic staging, necrosis, and American Joint Committee on Cancer grading were performed from hematoxylin and eosin sections. Immunohistochemistry and morphometry determined cellular infiltrate. Results Two pathologically complete, two major (> 50%), and four minor responses (> 30% but < 50%) resulted from LI treatment (overall response rate, 42%). Histopathology showed that the intratumoral CD4+:CD8+ ratio was low (< 1) in patients not treated with LI (controls). An increase in tumor-infiltrating CD4+ and a decrease of CD8+ T cells was observed in LI-treated patients, leading to a significantly (P < .05) higher intratumoral CD4+:CD8+ ratio (> 2.5). This was paralleled by dendritic cell transition from tumor surface toward stromal interface (P < .05), with macrophage decrease and neutrophil accumulation, multifocal microscopic necrosis, and significant (P < .05) increase in tumor stroma of LI-treated patients compared with controls. Conclusion LI-treated OSCC patients were characterized by a markedly altered composition of tumor-infiltrating mononuclear cells, increased CD4+:CD8+ ratio, and increased tumor stroma to epithelial ratio, all of which were distinct from controls. |
| Databáze: | OpenAIRE |
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