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.

中文翻译：

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Warburg免疫学效应：代谢肿瘤基质评分（MeTS）可以指导癌症免疫治疗吗？

“糖酵解开关”也称为“ Warburg效应”是肿瘤细胞的关键特征，并导致肿瘤环境中乳酸和质子的积累。有趣的是，非恶性淋巴细胞或基质细胞（如肿瘤相关的巨噬细胞和癌症相关的成纤维细胞）促进了乳酸在肿瘤环境中的蓄积，这种现象被称为“逆华伯格效应”。局部乳酸性酸中毒具有很强的免疫抑制作用，并介导肿瘤的免疫逃逸。然而，一些肿瘤不表现出Warburg表型，或者依赖于呼吸或者表现为具有不同代谢特性的细胞的镶嵌。基于这些发现以及T细胞浸润可预测患者预后的知识，我们建议使用代谢肿瘤基质评分来确定成功进行抗肿瘤免疫反应的可能性：（a）具有高T细胞浸润性（“热”）的呼吸道肿瘤；（b）具有呼吸道肿瘤细胞但糖酵解基质细胞的反向Warburg型；（c）具有糖酵解室和呼吸室的混合型；（d）具有低T细胞浸润的糖酵解性（Warburg）肿瘤（“冷”）。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，与预后相关，并且可能有助于选择适当的免疫疗法。（c）具有糖酵解室和呼吸室的混合型；（d）具有低T细胞浸润的糖酵解性（Warburg）肿瘤（“冷”）。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，与预后相关，并且可能有助于选择适当的免疫疗法。（c）具有糖酵解室和呼吸室的混合型；（d）具有低T细胞浸润的糖酵解性（Warburg）肿瘤（“冷”）。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，与预后相关，并且可能有助于选择适当的免疫疗法。