Lactate: A regulator of immune microenvironment and a clinical prognosis indicator in colorectal cancer

Abstract

Lactate can play an immunosuppressive role in the tumor microenvironment and promote tumor development by recruiting and inducing the activity of immunosuppressive cells and molecules. High lactate concentrations are important for tumor cell metastasis, angiogenesis, and treatment resistance. With the in-depth studies on tumor metabolism, lactate, one of the key factors involved in glycolysis, has been increasing emerged its characteristic clinical value in colorectal cancer (CRC). In this study, lactate genes were screened based on lactate metabolism pathways. Subsequently, the lactate subtypes were determined by clustering and analysis of the subtypes at all levels, including immune checkpoints, immune infiltration, and clinical characteristics, which revealed the biological significance of lactate metabolism in CRC. Subtype-based differential gene analysis resulted in a lactate score, which stratifies the prognosis of CRC. We discovered that 27 lactate genes and 61 lactate-phenotype genes are associated with immune cell infiltration and have a significant prognostic efficacy. The CRC patients were clustered into four subtypes and five clusters, based on lactate genes and lactate-phenotype genes, respectively. There are significant differences in survival time and activities of hallmark pathways, namely immune-related signatures and chemokines, among these subtypes and clusters. Particularly, cluster 2 and subtype 1 have significantly higher lactate scores than that of the others. In conclusion, lactate score is an independent prognostic factor for cancer that can be used as a clinical guide for predicting CRC progression and as an evaluation factor for the effect of immunotherapy in CRC.

From adenoma to CRC stages: the oral-gut microbiome axis as a source of potential microbial and metabolic biomarkers of malignancy

“…Finally, high lactate concentrations are important for tumor cell metastasis, angiogenesis, and treatment resistance. Of note, the lactate score has been recently shown as an independent prognostic factor for cancer that can be used as a clinical guide for predicting CRC progression and as an evaluation factor for immunotherapy effectiveness [60] . Interestingly, we also observed a positive correlation of Bifidobacterium with lactate, which further corroborates the predicted metagenomic pathway analysis.…”

Warburg effect‐related risk scoring model to assess clinical significance and immunity characteristics of glioblastoma

“…Recent research has demonstrated that elevated lactic acid produced by Warburg effect is a poor prognostic indicator for metastatic lung cancer 9 . The effect of lactate has also been established and confirmed in the prognosis of colorectal cancer, 10 lung adenocarcinoma, 11 and esophageal squamous cell carcinoma 12 . Moreover, recent research has demonstrated that Warburg effect‐related genes have a significant effect on tumor progression and prognosis.…”

Implication of Obesity and Gut Microbiome Dysbiosis in the Etiology of Colorectal Cancer

“…Another metabolite, lactate, can serve an immunosuppressive effect in the TME and promote tumor formation by attracting and stimulating the function of immunosuppressive molecules and cells [ 169 ]. It has been found to boost angiogenesis and provide oxygen and glucose to cancer cells, which in turn facilitates the growth, invasion, and migration of colon cells [ 169 ].…”

“…Another metabolite, lactate, can serve an immunosuppressive effect in the TME and promote tumor formation by attracting and stimulating the function of immunosuppressive molecules and cells [ 169 ]. It has been found to boost angiogenesis and provide oxygen and glucose to cancer cells, which in turn facilitates the growth, invasion, and migration of colon cells [ 169 ]. The lactate metabolized by cancerous cells exacerbates CRC progression by prompting macrophages to exhibit M2-type polarization and the production of high-mobility group box 1 (HMGB1), which is essential in maintaining nucleosome structure and controlling the transcription of many genes [ 170 ].…”