Yin Ting-Ting, Huang Meng-Xing, Wang Fei, Jiang Yi-Hua, Long Jie, Li Liang, Cao Jie
Department of General Surgery, Guangzhou Digestive Disease Center, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China.
Department of General Surgery, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, South China University of Technology, Guangzhou, China.
Front Genet. 2022 Aug 15;13:943849. doi: 10.3389/fgene.2022.943849. eCollection 2022.
Tumor-derived lactate can modulate the function of infiltrating immune cells to establish an immunosuppressive microenvironment that favors tumor progression. However, possible effects of lactate-related genes (LRGs) on the tumor microenvironment (TME) of breast cancer (BRCA) are still unknown. LRGs were comprehensively screened from lactate metabolism-related pathways. We correlated the expression of these LRGs with immune cell infiltrating characteristics in the TME and clinicopathological features of patients. We also established a lactate score for quantifying lactate metabolism patterns of cancers and to predict of recurrence-free survival (RFS). We successfully constructed a lactate score that was an independent prognostic factor in BRCA. A low lactate score, which was associated with immune activation with increased CD8 T cells infiltration levels, indicated an inflamed TME. Consistently, higher expression levels of inhibitory immune checkpoints, including PD-L1, LAG3, CTLA4, and TIM3, as observed from high lactate score subgroup, suggested an immune-desert phenotype as well as poor prognosis. Moreover, a low lactate score predicted the increased chemotherapeutic drug sensitivity and enhanced anti-PD-1 immunotherapy responses. The present study analyzed the potential roles of LRGs in the TME diversity and prognosis. These results will help to improve our understanding of the characteristics of TME immune cell infiltration and guide the development of more effective immunotherapy strategies.
肿瘤衍生的乳酸可以调节浸润性免疫细胞的功能，以建立有利于肿瘤进展的免疫抑制微环境。然而，乳酸相关基因（LRGs）对乳腺癌（BRCA）肿瘤微环境（TME）的潜在影响仍然未知。从乳酸代谢相关途径中全面筛选LRGs。我们将这些LRGs的表达与TME中的免疫细胞浸润特征以及患者的临床病理特征相关联。我们还建立了一个乳酸评分，用于量化癌症的乳酸代谢模式并预测无复发生存期（RFS）。我们成功构建了一个乳酸评分，它是BRCA的独立预后因素。低乳酸评分与免疫激活相关，CD8 T细胞浸润水平增加，表明TME呈炎症状态。一致地，从高乳酸评分亚组中观察到，包括PD-L1、LAG3、CTLA4和TIM3在内的抑制性免疫检查点的较高表达水平，提示免疫沙漠表型以及预后不良。此外，低乳酸评分预示着化疗药物敏感性增加和抗PD-1免疫治疗反应增强。本研究分析了LRGs在TME多样性和预后中的潜在作用。这些结果将有助于提高我们对TME免疫细胞浸润特征的理解，并指导更有效的免疫治疗策略的开发。
