Internal Medicine III, University Hospital Regensburg, Regensburg, Germany.
Institute of Pathology, University of Regensburg, Regensburg, Germany.
Immunol Rev. 2020 May;295(1):187-202. doi: 10.1111/imr.12846. Epub 2020 Mar 10.
The "glycolytic switch" also known as the "Warburg effect" is a key feature of tumor cells and leads to the accumulation of lactate and protons in the tumor environment. Intriguingly, non-malignant lymphocytes or stromal cells such as tumor-associated macrophages and cancer-associated fibroblasts contribute to the lactate accumulation in the tumor environment, a phenomenon described as the "Reverse Warburg effect." Localized lactic acidosis has a strong immunosuppressive effect and mediates an immune escape of tumors. However, some tumors do not display the Warburg phenotype and either rely on respiration or appear as a mosaic of cells with different metabolic properties. Based on these findings and on the knowledge that T cell infiltration is predictive for patient outcome, we suggest a metabolic-tumor-stroma score to determine the likelihood of a successful anti-tumor immune response: (a) a respiring tumor with high T cell infiltration ("hot"); (b) a reverse Warburg type with respiring tumor cells but glycolytic stromal cells; (c) a mixed type with glycolytic and respiring compartments; and (d) a glycolytic (Warburg) tumor with low T cell infiltration ("cold"). Here, we provide evidence that these types can be independent of the organ of origin, prognostically relevant and might help select the appropriate immunotherapy approach.
“糖酵解开关”也被称为“Warburg 效应”，是肿瘤细胞的一个关键特征，导致乳酸和质子在肿瘤环境中积累。有趣的是，非恶性淋巴细胞或基质细胞，如肿瘤相关巨噬细胞和癌相关成纤维细胞，有助于肿瘤环境中乳酸的积累，这种现象被描述为“反向 Warburg 效应”。局部乳酸酸中毒具有强烈的免疫抑制作用，并介导肿瘤的免疫逃逸。然而，一些肿瘤不显示 Warburg 表型，要么依赖呼吸，要么表现为具有不同代谢特性的细胞马赛克。基于这些发现以及 T 细胞浸润可预测患者预后的知识，我们建议采用代谢-肿瘤-基质评分来确定抗肿瘤免疫反应成功的可能性：(a) 富含 T 细胞浸润的呼吸型肿瘤（“热”型）；(b) 具有呼吸型肿瘤细胞但糖酵解基质细胞的反向 Warburg 型；(c) 具有糖酵解和呼吸区室的混合型；以及 (d) 低 T 细胞浸润的糖酵解（Warburg）型肿瘤（“冷”型）。在这里，我们提供的证据表明，这些类型可以独立于起源器官，具有预后相关性，并可能有助于选择合适的免疫治疗方法。
