Tímár József, Ladányi Andrea, Forster-Horváth Csaba, Lukits Júlia, Döme Balázs, Remenár Eva, Godény Mária, Kásler Miklós, Bencsik Beáta, Répássy Gábor, Szabó György, Velich Norbert, Suba Zsuzsa, Elo János, Balatoni Zsuzsa, Pócza Károly, Zemplén Béla, Chretien Paul, Talor Eyal
National Institute of Oncology, Department of Otolaryngology and Head and Neck Surgery, Semmelweis University, Budapest, Hungary.
J Clin Oncol. 2005 May 20;23(15):3421-32. doi: 10.1200/JCO.2005.06.005.
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.
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.
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.
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.
研究局部新辅助白细胞介素注射（LI）方案对口腔鳞状细胞癌（OSCC）患者的临床病理影响。治疗方案包括：作为白细胞介素-2（IL-2）的LI 800 IU/天，每周5次，分3周进行，一半经瘤周注射，一半经淋巴周注射；低剂量环磷酰胺；吲哚美辛；锌；以及多种维生素。
39例诊断为T2-3N0-2M0 OSCC的患者参与了此项II期多中心研究的病理部分（19例接受LI治疗的患者和20例历史对照）。通过影像学确定临床反应。所有患者在手术时获取石蜡包埋的肿瘤样本。LI治疗组在治疗结束后14至54天之间进行手术。从苏木精和伊红切片进行组织学评估、病理分期、坏死情况以及美国癌症联合委员会分级。免疫组织化学和形态计量学确定细胞浸润情况。
LI治疗产生了2例病理完全缓解、2例主要缓解（> 50%）和4例次要缓解（> 30%但< 50%）（总缓解率为42%）。组织病理学显示，未接受LI治疗的患者（对照组）瘤内CD4+:CD8+比值较低（< 1）。在接受LI治疗的患者中观察到肿瘤浸润性CD4+增加以及CD8+ T细胞减少，导致瘤内CD4+:CD8+比值显著升高（P < .05）（> 2.5）。与此同时，树突状细胞从肿瘤表面向基质界面转变（P < .05），巨噬细胞减少而中性粒细胞积聚，出现多灶性微小坏死，与对照组相比，接受LI治疗的患者肿瘤基质显著增加（P < .05）。
接受LI治疗的OSCC患者的特征是肿瘤浸润性单核细胞组成明显改变、CD4+:CD8+比值增加以及肿瘤基质与上皮比值增加，所有这些均与对照组不同。
