Linking Immunoevasion and Metabolic Reprogramming in B-Cell-Derived Lymphomas.
Linking Immunoevasion and Metabolic Reprogramming in B-Cell-Derived Lymphomas.
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DOI：
10.3389/fonc.2020.594782
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发表时间：
2020
影响因子：
4.7
通讯作者：
Mougiakakos D
中科院分区：
文献类型：
--
作者：
Böttcher M;Baur R;Stoll A;Mackensen A;Mougiakakos D
淋巴瘤代表了由淋巴细胞产生的多种恶性肿瘤。尽管 B 细胞起源淋巴瘤的诊断和治疗取得了进步，但复发性和难治性疾病的临床需求仍未得到满足。因此，更好地了解淋巴瘤的内在特征以及与其细胞微环境的相互作用对于开发新的治疗策略至关重要。事实上，基于免疫的方法的作用正在稳步增强，其中包括使用抗肿瘤抗原的单克隆抗体、免疫检查点抑制剂，甚至转基因 T 细胞。代谢重编程和免疫逃逸都代表了公认的癌症标志。奥托·瓦尔堡 (Otto Warburg) 在 20 世纪初提出的肿瘤代谢可促进生存、增殖和治疗耐药性。同时，恶性细胞利用多种机制来逃避免疫监视。越来越多的证据表明，代谢重编程不仅赋予肿瘤细胞内在的生长和生存优势，而且还影响局部和全身的抗肿瘤免疫。肿瘤和免疫细胞竞争对免疫细胞功能至关重要的碳水化合物或氨基酸等营养物质。此外，恶性细胞中代谢途径的扭曲会导致生物活性代谢物的大量产生和释放，例如乳酸、犬尿氨酸或活性氧（ROS），从而影响免疫细胞的健康和功能。肿瘤微环境的这种“代谢重塑”将抗肿瘤免疫反应转向耐受性。在这里，我们将回顾导致 B 细胞淋巴瘤代谢改变的分子事件及其对抗肿瘤免疫的影响。
Lymphomas represent a diverse group of malignancies that emerge from lymphocytes. Despite improvements in diagnosis and treatment of lymphomas of B-cell origin, relapsed and refractory disease represents an unmet clinical need. Therefore, it is of utmost importance to better understand the lymphomas’ intrinsic features as well as the interactions with their cellular microenvironment for developing novel therapeutic strategies. In fact, the role of immune-based approaches is steadily increasing and involves amongst others the use of monoclonal antibodies against tumor antigens, inhibitors of immunological checkpoints, and even genetically modified T-cells. Metabolic reprogramming and immune escape both represent well established cancer hallmarks. Tumor metabolism as introduced by Otto Warburg in the early 20th century promotes survival, proliferation, and therapeutic resistance. Simultaneously, malignant cells employ a plethora of mechanisms to evade immune surveillance. Increasing evidence suggests that metabolic reprogramming does not only confer cell intrinsic growth and survival advantages to tumor cells but also impacts local as well as systemic anti-tumor immunity. Tumor and immune cells compete over nutrients such as carbohydrates or amino acids that are critical for the immune cell function. Moreover, skewed metabolic pathways in malignant cells can result in abundant production and release of bioactive metabolites such as lactic acid, kynurenine or reactive oxygen species (ROS) that affect immune cell fitness and function. This “metabolic re-modeling” of the tumor microenvironment shifts anti-tumor immune reactivity toward tolerance. Here, we will review molecular events leading to metabolic alterations in B-cell lymphomas and their impact on anti-tumor immunity.
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影响因子：
29
作者：
Cascone T;McKenzie JA;Mbofung RM;Punt S;Wang Z;Xu C;Williams LJ;Wang Z;Bristow CA;Carugo A;Peoples MD;Li L;Karpinets T;Huang L;Malu S;Creasy C;Leahey SE;Chen J;Chen Y;Pelicano H;Bernatchez C;Gopal YNV;Heffernan TP;Hu J;Wang J;Amaria RN;Garraway LA;Huang P;Yang P;Wistuba II;Woodman SE;Roszik J;Davis RE;Davies MA;Heymach JV;Hwu P;Peng W
通讯作者：
Peng W
影响因子：
4.7
作者：
Galicia-Vázquez G;Aloyz R
通讯作者：
Aloyz R
影响因子：
64.8
作者：
Alizadeh, AA;Eisen, MB;Staudt, LM
通讯作者：
Staudt, LM
影响因子：
4
作者：
Gooptu M;Whitaker-Menezes D;Sprandio J;Domingo-Vidal M;Lin Z;Uppal G;Gong J;Fratamico R;Leiby B;Dulau-Florea A;Caro J;Martinez-Outschoorn U
通讯作者：
Martinez-Outschoorn U
影响因子：
29
作者：
Angelin A;Gil-de-Gómez L;Dahiya S;Jiao J;Guo L;Levine MH;Wang Z;Quinn WJ 3rd;Kopinski PK;Wang L;Akimova T;Liu Y;Bhatti TR;Han R;Laskin BL;Baur JA;Blair IA;Wallace DC;Hancock WW;Beier UH
通讯作者：
Beier UH