Zahoor Haris, Pavicic Paul G, Przybycin Christopher, Ko Jennifer, Stephens Lisa, Radivoyevitch Tomas, Jia Xuefei, Diaz-Montero Claudia Marcela, Finke James, Rayman Patricia A, Gilligan Timothy D, Grivas Petros, Ornstein Moshe, Garcia Jorge A, Rini Brian I
Taussig Cancer Institute Department of Immunology, Lerner Research Institute Robert J. Tomsich Pathology and Laboratory Medicine Institute Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH University of Washington, Seattle, WA.
Medicine (Baltimore). 2018 Sep;97(37):e12344. doi: 10.1097/MD.0000000000012344.
T cell infiltration in tumors has been investigated as a biomarker of response to checkpoint inhibitors. Neo-adjuvant studies in renal cell carcinoma (RCC) may provide a unique opportunity to compare T cell infiltration in a pretreatment renal mass biopsy to a posttreatment nephrectomy specimen, and thus evaluate the effects of immune checkpoint inhibitors. However, there are no data regarding the association of T cell infiltration in matched biopsy and nephrectomy samples without intervening treatment. Understanding this association will inform investigation of this potential biomarker in future studies.Matched biopsy and nephrectomy samples (without intervening systemic therapy) were identified from patients with nonmetastatic RCC. Selected tissue sections from biopsy and nephrectomy samples were reviewed and marked for intratumoral lymphocytes by a pathologist. Immunohistochemistry (IHC) was utilized to stain for T cell markers (CD3, CD4, and CD8). Intratumoral staining was then quantified in the tissue sections as counts per total tumor area surveyed. Spearman correlation (r) was used to measure associations.Thirty matched pairs were investigated. The median interval between biopsy and nephrectomy was 2.8 (0.2-87.7) months. Clear cell was the most common histology (29/30; 97%). There was a statistically significant positive correlation between the frequency of CD3 and CD8 T cells between matched biopsy and nephrectomy samples (r = 0.39; P = .036 and r = 0.38; P = .041, respectively).The frequencies of CD8+ T cells in matched biopsy and nephrectomy samples in RCC in the absence of intervening treatment have been characterized and show a positive correlation between matched biopsy and nephrectomy samples.
肿瘤中的T细胞浸润已被作为检查点抑制剂反应的生物标志物进行研究。肾细胞癌(RCC)的新辅助研究可能提供一个独特的机会,来比较治疗前肾肿块活检组织与治疗后肾切除标本中的T细胞浸润情况,从而评估免疫检查点抑制剂的效果。然而,目前尚无关于未经干预治疗的配对活检和肾切除样本中T细胞浸润相关性的数据。了解这种关联将为未来研究中对这一潜在生物标志物的研究提供参考。从非转移性RCC患者中识别出配对的活检和肾切除样本(未进行干预性全身治疗)。病理学家对活检和肾切除样本中选定的组织切片进行复查,并标记肿瘤内淋巴细胞。利用免疫组织化学(IHC)对T细胞标志物(CD3、CD4和CD8)进行染色。然后在组织切片中对肿瘤内染色进行定量,以每单位总肿瘤面积中的细胞计数表示。采用Spearman相关性分析(r)来衡量相关性。共研究了30对配对样本。活检和肾切除之间的中位间隔时间为2.8(0.2 - 87.7)个月。透明细胞是最常见的组织学类型(29/30;97%)。配对活检和肾切除样本之间CD3和CD8 T细胞频率存在统计学显著的正相关性(r分别为0.39;P = 0.036和r为0.38;P = 0.041)。对未进行干预治疗的RCC患者配对活检和肾切除样本中CD8 + T细胞频率进行了特征分析,结果显示配对活检和肾切除样本之间呈正相关。