Updates on Immunotherapy and Immune Landscape in Renal Clear Cell Carcinoma.
Updates on Immunotherapy and Immune Landscape in Renal Clear Cell Carcinoma.
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DOI：
10.3390/cancers13225856
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发表时间：
2021-11-22
期刊：
影响因子：
5.2
通讯作者：
Zhang W
中科院分区：
文献类型：
--
作者：
Kim MC;Jin Z;Kolb R;Borcherding N;Chatzkel JA;Falzarano SM;Zhang W
透明细胞肾细胞癌（ccRCC）具有多种独特的免疫学特征，包括高度的免疫浸润和相对较低的突变负荷、对细胞毒性化疗的抵抗性以及对抗血管生成治疗和免疫治疗的相对敏感性。免疫检查点抑制剂 (ICI) 疗法已成为 ccRCC 治疗的标准护理，但需要更好地了解 ccRCC 的分子和细胞特征，才能真正优化 ICI 疗法的使用。我们重点关注癌症免疫学，总结了 ccRCC 中 ICI 的临床试验、这些临床试验的分子和细胞相关性以及单细胞 RNA 测序研究，以全面概述 ccRCC 肿瘤微环境中的免疫状况，特别是在 ICI 治疗的背景下。我们将讨论可用于预测 ccRCC 患者治疗反应的潜在分子和细胞生物标志物。透明细胞肾细胞癌 (ccRCC) 的一些临床病理学特征有助于形成“非典型”癌症，包括对化疗的耐药性、对抗血管生成治疗和 ICI 的敏感性（尽管突变负荷较低），以及 CD8+ T 细胞浸润是不良预后的预测因子——通常 CD8+ T 细胞浸润是癌症患者的良好预后因素。这些“非典型”特征促使研究人员研究导致 T 细胞浸润增加（尽管分子负担相对较低）的分子和免疫机制，并破译导致对 ICI 更好反应的免疫景观。在本研究中，我们总结了过去和正在进行的 ccRCC 免疫疗法的关键临床试验，强调导致 ICI 疗法成功或失败的潜在分子和细胞机制。 ccRCC 的单细胞分析提供了对肿瘤免疫微环境更全面、更详细的了解，并促进了从肿瘤浸润免疫细胞中发现分子生物标志物。本文将重点讨论 ccRCC 中的一些主要免疫细胞，包括 T 细胞和肿瘤相关巨噬细胞 (TAM)。我们将进一步提供一些关于使用源自这些免疫细胞类型的分子和细胞生物标志物来潜在提高 ccRCC 患者对 ICI 的反应率的观点。
Clear cell renal cell carcinomas (ccRCC) have several distinct immunological features, including a high degree of immune infiltration and relatively low mutational burdens, the resistance to cytotoxic chemotherapy, and relative sensitivity to anti-angiogenic therapy and immunotherapies. Immune checkpoint inhibitor (ICI) therapy has become standard care in the treatment of ccRCC, but a better understanding of the molecular and cellular characteristics of ccRCC is needed to truly optimize the use of ICI therapy. With a focus on cancer immunology, we summarize the clinical trials of ICIs in ccRCC, the molecular and cellular correlates of these clinical trials, and the single-cell RNA sequencing studies to provide a comprehensive overview of the immune landscape within the ccRCC tumor microenvironment, in particular in the context of ICI therapy. We will discuss potential molecular and cellular biomarkers that can be used to predict therapeutic responses in ccRCC patients. Several clinicopathological features of clear cell renal cell carcinomas (ccRCC) contribute to make an “atypical” cancer, including resistance to chemotherapy, sensitivity to anti-angiogenesis therapy and ICIs despite a low mutational burden, and CD8+ T cell infiltration being the predictor for poor prognosis–normally CD8+ T cell infiltration is a good prognostic factor in cancer patients. These “atypical” features have brought researchers to investigate the molecular and immunological mechanisms that lead to the increased T cell infiltrates despite relatively low molecular burdens, as well as to decipher the immune landscape that leads to better response to ICIs. In the present study, we summarize the past and ongoing pivotal clinical trials of immunotherapies for ccRCC, emphasizing the potential molecular and cellular mechanisms that lead to the success or failure of ICI therapy. Single-cell analysis of ccRCC has provided a more thorough and detailed understanding of the tumor immune microenvironment and has facilitated the discovery of molecular biomarkers from the tumor-infiltrating immune cells. We herein will focus on the discussion of some major immune cells, including T cells and tumor-associated macrophages (TAM) in ccRCC. We will further provide some perspectives of using molecular and cellular biomarkers derived from these immune cell types to potentially improve the response rate to ICIs in ccRCC patients.
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影响因子：
5.9
作者：
Borcherding N;Vishwakarma A;Voigt AP;Bellizzi A;Kaplan J;Nepple K;Salem AK;Jenkins RW;Zakharia Y;Zhang W
通讯作者：
Zhang W
影响因子：
50.3
作者：
Au L;Hatipoglu E;Robert de Massy M;Litchfield K;Beattie G;Rowan A;Schnidrig D;Thompson R;Byrne F;Horswell S;Fotiadis N;Hazell S;Nicol D;Shepherd STC;Fendler A;Mason R;Del Rosario L;Edmonds K;Lingard K;Sarker S;Mangwende M;Carlyle E;Attig J;Joshi K;Uddin I;Becker PD;Sunderland MW;Akarca A;Puccio I;Yang WW;Lund T;Dhillon K;Vasquez MD;Ghorani E;Xu H;Spencer C;López JI;Green A;Mahadeva U;Borg E;Mitchison M;Moore DA;Proctor I;Falzon M;Pickering L;Furness AJS;Reading JL;Salgado R;Marafioti T;Jamal-Hanjani M;PEACE Consortium;Kassiotis G;Chain B;Larkin J;Swanton C;Quezada SA;Turajlic S;TRACERx Renal Consortium
通讯作者：
TRACERx Renal Consortium
影响因子：
82.9
作者：
Choueiri, Toni K.;Kaelin, William G., Jr.
通讯作者：
Kaelin, William G., Jr.
DOI：
10.1158/1078-0432.ccr-19-2838
发表时间：
2020-06-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Atkins MB;Rini BI;Motzer RJ;Powles T;McDermott DF;Suarez C;Bracarda S;Stadler WM;Donskov F;Gurney H;Oudard S;Uemura M;Lam ET;Grüllich C;Quach C;Carroll S;Ding B;Zhu QC;Piault-Louis E;Schiff C;Escudier B
通讯作者：
Escudier B
影响因子：
48
作者：
Amezquita, Robert A.;Lun, Aaron T. L.;Hicks, Stephanie C.
通讯作者：
Hicks, Stephanie C.