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Abstract

It becomes exceedingly clear that immune cells not only use cellular metabolism to meet their bioenergetic demands, but that these metabolic pathways also determine their phenotype and function. We now also acknowledge that perturbations of distinct metabolic networks are implicated in immune cell-associated diseases. "Immunometabolism" explores the metabolic machinery in all immune subsets and studies how it regulates their immunological function in either homeostatic or pathological situations. A distinct metabolic status between pro-inflammatory M1 and anti-inflammatory M2 macrophages has already been unraveled. Similar to the Warburg effect observed in cancer cells, M1 macrophages mainly use glucose consumption and lactate excretion, whereas M2 macrophages mostly rely on a combination of oxidative phosphorylation (OXPHOS), fatty acid oxidation (FAO) and mitochondrial respiration. In T lymphocytes, a similar shift in cellular metabolism could be observed in inflammatory T helper 17 (Th17) cells, performing aerobic glycolysis and glutamine oxidation, and regulatory T cells (Treg), primarily depending on mitochondrial oxidative pathways to meet their energy needs [1]. Until recently, such perceptions on energy metabolism reprogramming were provocative as researchers assumed that cells would only rely on glycolysis when their mitochondria were impaired or oxygen was absent. Moreover, these hallmark studies highlighted the significance of cellular metabolism in the regulation of gene transcription and of metabolic enzymes in the control of protein translation and entire immunological processes such as differentiation and proliferation.

Wnt/β-Catenin signaling pathway in hepatocellular carcinoma: pathogenic role and therapeutic target

“…Numerous studies have shown that the Wnt/β-catenin signaling pathway plays an important role in regulating HCC cell proliferation, invasion and metastasis. Cripto-1 was found to be highly expressed in about 50% of HCC tissues ( 121 ). It can bind to the FZD7/LRP6 receptor and DVL3 and stabilize the expression of DVL3.…”

<p>Clinical Applications of Cerebrospinal Fluid Circulating Tumor DNA as a Liquid Biopsy for Central Nervous System Tumors</p>

“…Tumor mutational burden (TMB), as detected by tissue NGS, is a potential predictor of immunotherapy response. 101 Still, tissue biopsy of CNS tumors is invasive, making it non-ideal. A recent study published in Clinical Cancer Research confirmed that there is a correlation between high alteration number detection in ctDNA and improved response following immunotherapy; 102 supporting the use of ctDNA in place of tissue biopsy.…”

LTX-315 triggers anticancer immunity by inducing MyD88-dependent maturation of dendritic cells

“…LTX-315 is a synthetic 9-mer cationic oncolytic peptide developed as an analogue of bovine lactoferricin ( 5 , 6 ), which was selected from a series of chemically modified lactoferricin-derived lytic peptides because it displayed superior anticancer activity and lower toxicity on normal cells ( 5 ). LTX-315 induces tumor cell death by rapidly damaging cell membrane integrity ( 6 , 7 ) and permeabilizing mitochondrial membrane ( 8 , 9 ). Intra-tumoral administration of LTX-315 stimulates the generation of systemic tumor-specific immune responses ( 10 , 11 ), resulting in increased infiltration of cytotoxic CD8 + T cells and decreased regulatory T (Treg) cell infiltration in primary treated tumors ( 11 – 14 ) and in re-challenged secondary tumors ( 10 ).…”

“…For tumor-infiltrating DCs (TiDCs) to traffic to dLNs for the induction of antitumor immune responses, they must mature and acquire the necessary features capable of sufficiently triggering the activation of specific T cells. Given the release of multiple damage-associated molecular patterns (DAMPs) and alarmins (ATP, HMGB1, etc) by tumor cells treated with LTX-315 in vitro ( 8 , 10 , 11 ) and the known capacities of DAMPs/alarmins to induce DC maturation ( 19 , 20 ), it has been proposed that the DAMPs/alarmins released by LTX-315-treated tumor cells are responsible for triggering the maturation of TiDCs and subsequent tumor-specific immune response ( 6 ). We therefore sought to investigate whether and how LTX-315 induces DC maturation in the context of the generation of anti-melanoma immunity.…”