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。
英文原题:Patterns of Tumor Infiltrating Lymphocytes in Adenoid Cystic Carcinoma of the Head and Neck.
预后仍然较差,晚期复发常在5年及以后发生。
腺样囊性癌(ACC)是一种罕见的头颈部恶性肿瘤。其预后仍然较差,且常在5年及以后出现晚期复发。迄今为止,ACC尚无可靠的预后标志物。在多种实体瘤中,三级淋巴结构(TLS)与生存改善相关。本研究旨在探讨肿瘤浸润免疫细胞(TIL)的分布模式在ACC中的作用。研究纳入了来自三个不同癌症中心的50例患者队列进行分析。切片进行CD3、CD4、CD8和CD20染色,并评估其TIL分布情况。分布模式被确定为浸润-排斥型、浸润-炎症型以及存在三级淋巴结构。约半数病例表现为浸润-排斥型TIL模式,仅少数6例在肿瘤内存在TLS。在炎症型表型中,CD3+细胞是迄今为止最丰富的淋巴细胞亚型,且在该区域中,CD8+ T细胞占主导地位。任何TIL模式对总生存期或无病生存期均无影响。这表明ACC是一种免疫原性极低的肿瘤,即使淋巴细胞数量丰富似乎也不能改善该疾病的预后。因此,观察到的对免疫治疗缺乏反应并不令人意外,必须寻找其他方法来诱导免疫系统对ACC的识别。
Adenoid cystic carcinoma (ACC) is a rare malignancy in the head and neck. The prognosis remains poor and late recurrences often occur after 5 years and later. To date, there are no reliable prognostic markers for ACC. In several solid tumors, tertiary lymphoid structures (TLS) are associated with improved survival. This study aims to investigate the role of distribution patterns of tumor infiltrating immune cells (TIL) in ACC. A cohort of 50 patients from three different cancer centers was available for analysis. Sections were stained for CD3, CD4, CD8 and CD20 and evaluated with regard to their distribution of TIL. Patterns were determined as infiltrated-excluded, infiltrated-inflamed and presence of tertiary lymphoid structures. About half of the cases showed an infiltrated-excluded TIL pattern and only a minority of six cases had TLS present within the tumor. Within the inflamed phenotype CD3+ cells were by far the most abundant lymphocyte subtype, and within this compartment, CD8+ T cells were predominant. There was no influence on overall or disease-free survival by any of the TIL patterns. This indicates that ACC is a tumor with very low immunogenicity and even abundance of lymphocytes does not seem to improve prognosis for this disease. Therefore, the observed lack of response towards immunotherapy is not surprising and other methods to induce recognition of ACC by the immune system must be found.
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