Davis Dale, Tretiakova Maria S, Kizzar Chris, Woltjer Randy, Krajbich Victoria, Tykodi Scott S, Lanciault Christian, Andeen Nicole K
Oregon Health & Science University, Department of Pathology, Portland, OR 97239, United States of America.
University of Washington, Department of Pathology, Seattle, WA 98195, United States of America.
Ann Diagn Pathol. 2020 Aug;47:151537. doi: 10.1016/j.anndiagpath.2020.151537. Epub 2020 May 19.
Studies assessing tumor-infiltrating lymphocytes (TILs) in clear cell renal cell carcinoma (ccRCC) and clinical outcomes have mixed results. Given fundamental interaction of MHC class I with CD8+ T-cells, we hypothesized that expression of MHC class I associated protein, beta-2-microglobulin (B2M), may be an important immunologic marker in RCC. We sought to understand potential implications of CD8 + TILs and tumor B2M expression on overall survival and response to high-dose interleukin-2 (IL-2) therapy, in a cohort of patients with high-stage (clinical stage III and IV) ccRCC. Four tumor regions from 56 patients with ccRCC were retrospectively assessed immunohistochemically. At a median follow-up time of 33 months, 22 (39%) patients had died of disease, 23 (41%) were alive disease, and 11 (20%) had no evidence of disease. Tumors with high CD8 + TILs had a significantly lower death rate [hazard ratio (HR): 0.33, p = 0.02]. CD8 + TILs correlated with B2M expression (p = 0.007). On multivariable analyses, patients with both high B2M and CD8 + TILs had lower death rate (HR: 0.27, p = 0.03). Within the subgroup treated with IL-2 (n = 27, 48%), tumors with high CD8 + TILs were more likely to respond to IL-2 therapy [coefficient (coef): 1.6, p = 0.05]. On multivariable analyses, tumors with a combination of both high B2M expression and high CD8 + TILs also showed trend to responding to IL-2 therapy (coef: 2.5, p = 0.06). In conclusion, abundant CD8+ TILs and high tumor expression of beta-2-microglobulin were good prognostic indicators associated with longer survival in patients with high-stage ccRCC. Abundant CD8+ TILs may predict response to IL-2 therapy.
评估透明细胞肾细胞癌（ccRCC）中肿瘤浸润淋巴细胞（TILs）与临床结局的研究结果不一。鉴于MHC I类分子与CD8 + T细胞的基本相互作用，我们推测MHC I类相关蛋白β2微球蛋白（B2M）的表达可能是RCC中一种重要的免疫标志物。我们试图了解在一组高分期（临床III期和IV期）ccRCC患者中，CD8 + TILs和肿瘤B2M表达对总生存期及高剂量白细胞介素-2（IL-2）治疗反应的潜在影响。对56例ccRCC患者的四个肿瘤区域进行了回顾性免疫组化评估。在中位随访时间33个月时，22例（39%）患者死于疾病，23例（41%）患者疾病存活，11例（20%）患者无疾病证据。CD8 + TILs水平高的肿瘤死亡率显著更低[风险比（HR）：0.33，p = 0.02]。CD8 + TILs与B2M表达相关（p = 0.007）。多变量分析显示，B2M水平高且CD8 + TILs水平高的患者死亡率更低（HR：0.27，p = 0.03）。在接受IL-2治疗的亚组（n = 27，48%）中，CD8 + TILs水平高的肿瘤更有可能对IL-2治疗产生反应[系数（coef）：1.6，p = 0.05]。多变量分析显示，B2M表达水平高且CD8 + TILs水平高的肿瘤对IL-2治疗也有反应趋势（coef：2.5，p = 0.06）。总之，丰富的CD8 + TILs和肿瘤β2微球蛋白高表达是高分期ccRCC患者生存期延长的良好预后指标。丰富的CD8 + TILs可能预测对IL-2治疗的反应。
