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:Prognostic and Predictive Relevance of Tumor-Infiltrating Lymphocytes in Squamous Cell Head-Neck Cancer Patients Treated with Radical Radiotherapy/Chemo-Radiotherapy.
Prognostic and Predictive Relevance of Tumor-Infiltrating Lymphocytes in Squamous Cell Head-Neck Cancer Patients Treated with Radical Radiotherapy/Chemo-Radiotherapy.
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肿瘤微环境条件决定细胞毒性淋巴细胞进入肿瘤并存活的能力,从而促进或阻止免疫介导的癌细胞死亡。我们在一组头颈部鳞状细胞癌(HNSCC)中,研究TIL(肿瘤浸润淋巴细胞)密度对放疗结局的影响,并评估缺氧标志物与TIL密度之间的关系。分析了121例前瞻性接受根治性放疗/放化疗的HNSCC患者。放疗前在活检苏木精-伊红切片上评估TIL密度。TIL密度范围为每40倍视野0.8至150个淋巴细胞(中位数27.5)。按中位数将患者分为TIL低密度组和高密度组。早期T分期肿瘤的TIL密度显著较高(p<0.003),但与N分期无相关性。HIF1、HIF2和CA9过表达均与TIL浸润较差显著相关(p<0.03)。TIL密度高与疾病特异性总生存期较好、局部区域无复发生存改善显著相关(分别p=0.008和0.02),多变量分析也证实这一结果。结论是,允许淋巴细胞在瘤内聚集的HNSCC表型,在根治性放疗/放化疗后结局更好。瘤内活化的HIF和CA9相关通路是免疫“冷”肿瘤的特征,可能成为治疗干预靶点。
Microenvironmental conditions control the entrance and thriving of cytotoxic lymphocytes in tumors, allowing or preventing immune-mediated cancer cell death.
We investigated the role of tumor-infiltrating lymphocyte (TIL) density in the outcome of radiotherapy in a series of squamous cell head neck tumors (HNSCC).
Moreover, we assessed the link between markers of hypoxia and TIL density. One-hundred twenty-one patients with HNSCC treated prospectively with radical radiotherapy/chemo-radiotherapy were analyzed. The assessment of TIL density was performed on hematoxylin and eosin biopsy sections before radiotherapy. TIL density ranged from 0. 8 to 150 lymphocytes per 40 optical field (median 27. 5). Using the median value, patients were grouped into two categories of low and high TIL density. Early T-stage tumors had a significantly higher TIL density (p < 0. 003), but we found no association with N-stage.
Overexpression of HIF1 , HIF2 , and CA9 was significantly linked with poor infiltration by TILs (p < 0. 03). A significant association of high TIL density with better disease-specific overall survival and improved locoregional relapse-free survival was noted (p = 0. 008 and 0. 02, respectively), which was also confirmed in multivariate analysis.
It is concluded that HNSCC phenotypes that allow for the intratumoral accumulation of lymphocytes have a better outcome following radical radiotherapy/chemo-radiotherapy. Intratumoral-activated HIF- and CA9-related pathways characterize immunologically cold tumors and may be used as targets for therapeutic interventions.
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