帕博利珠单抗联合二甲双胍治疗转移性头颈部癌的 II 期可行性研究
A Phase II Feasibility Study Combining Pembrolizumab and Metformin in Patients with Metastatic Head and Neck Cancer.
二甲双胍联合帕博利珠单抗耐受性良好,仅出现轻度胃肠道不良事件,并展现出有前景的活性,值得在随机试验中进一步研究。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Tumor Infiltration Levels of CD3, Foxp3 (+) Lymphocytes and CD68 Macrophages at Diagnosis Predict 5-Year Disease-Specific Survival in Patients with Oropharynx Squamous Cell Carcinoma.
Tumor Infiltration Levels of CD3, Foxp3 (+) Lymphocytes and CD68 Macrophages at Diagnosis Predict 5-Year Disease-Specific Survival in Patients with Oropharynx Squamous Cell Carcinoma.
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头颈癌(HNC)是全球第六常见癌症。口咽癌(OP)尤其值得关注,因为可能存在与预后相关的HPV感染。炎症细胞浸润肿瘤的程度可能随预后而异。
我们旨在研究肿瘤中TIL(肿瘤浸润淋巴细胞)和肿瘤相关巨噬细胞(TAM)数量是否与HPV状态相关,并能否预测5年疾病特异性生存期(DSS)。对170例接受口咽癌治疗患者的福尔马林固定、石蜡包埋(FFPE)活检切片进行免疫组化染色,评估CD68+ TAM、CD3+和Foxp3+(调节性T细胞)TIL数量。利用FFPE切片通过PCR检测HPV,并以免疫组化检测p16。根据既往发表的方法,在FFPE苏木精-伊红切片中评估肿瘤细胞核多形性、肿瘤侵袭、促结缔组织增生和炎症水平。与HPV阴性患者相比,HPV阳性患者的CD3+ TIL和Foxp3+ TIL水平均较高。Foxp3+ TIL和CD68+巨噬细胞水平高,预测5年DSS较好。Foxp3+ TIL水平的预测作用独立于年龄、性别、TNM分期、HPV感染、间质促结缔组织增生水平、肿瘤侵袭和核多形性;且在HPV阳性患者中的作用较HPV阴性患者更明显。
Head and neck cancer (HNC) is the sixth most common cancer worldwide. Oropharyngeal (OP) cancers are of special interest because of possible underlying HPV infection which is tied to prognosis. Influxes of inflammatory cells into tumors may vary with prognoses.
We wanted to study whether the number of tumor-infiltrating lymphocytes (TIL) and tumor-associated macrophages (TAM) in tumors correlated to HPV status and predicted 5-year disease-specific survival (DSS). Formalin-fixed paraffin-embedded (FFPE) biopsies cut sections from 170 patients treated for OP cancer were stained by immunohistochemistry and evaluated for the number of CD68 (+) TAMs, CD3 (+), and Foxp3 (+) (T regulatory) TILs. From FFPE slides HPV by PCR and p16 by immunohistochemistry were established.
From FFPE Hematoxylin-Eosin slides, levels of tumor nuclear polymorphism, tumor invasion, desmoplasia, and inflammation were determined as previously published. Levels of TIL CD3 (+) and TIL Foxp3 (+) were increased among the HPV (+) compared to the HPV (-) patients.
High levels of TIL Foxp3 (+) and CD68 (+) macrophages predicted better 5-year DSS. TIL Foxp3 (+) levels predicted independent of age, gender, TNM stage, and HPV infection as well as level of stromal desmoplasia, tumor invasion, and nuclear polymorphism, but more pronounced among tumor HPV (+) than HPV (-) patients.
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