Core Viewpoint - The study reveals that targeting dihydroorotate dehydrogenase (DHODH) to inhibit macropinocytosis in tumor cells is a potential method to reverse immunosuppression and improve cancer immunotherapy [8]. Group 1: Key Findings - High-throughput screening identified DHODH as essential for cancer cell macropinocytosis [6]. - DHODH maintains the O-GlcNAc glycosylation modification and membrane localization of neuropilin-1 (NRP1), promoting macropinocytosis [6]. - Macropinocytosis increases the acetylation of transcription factor CIITA, leading to the suppression of major histocompatibility complex class II (MHC II) expression, thereby facilitating immune evasion [6]. Group 2: Implications for Immunotherapy - Inhibition of DHODH in cancer cells significantly enhances immune cell infiltration and activates anti-tumor immune responses, overcoming resistance to anti-PD-1 therapy [5][6]. - High expression levels of DHODH and NRP1 in human breast and lung cancer tissues correlate with poor patient prognosis [5].

Core Viewpoint - Recent studies reveal that taurine, a common ingredient in energy drinks, plays a significant role in leukemia progression by driving glycolysis in the tumor microenvironment, suggesting caution in its supplementation for leukemia patients [2][9]. Group 1: Taurine's Role in Leukemia - A study from the University of Rochester indicates that taurine from the tumor niche promotes glycolysis, facilitating leukemia development [2]. - The research utilized single-cell RNA sequencing to identify molecular interactions between the bone marrow microenvironment and leukemia stem cells (LSC), highlighting the importance of these interactions in leukemia progression [5]. - Taurine biosynthesis driven by cysteine dioxygenase-1 (CDO1) is limited to osteoblast lineage cells and increases during myeloid disease progression, with LSC relying on taurine transport proteins for their growth [5][6]. Group 2: Implications for Treatment - Inhibition of taurine transport proteins significantly suppresses the progression of acute myeloid leukemia (AML) in mouse models and human patient-derived cells [6]. - Elevated expression of taurine transport proteins in venetoclax-resistant AML patients suggests a potential therapeutic target, as inhibiting these proteins can enhance the efficacy of existing treatments [6]. - The study indicates that taurine uptake deficiency reduces leukemia stem cell capabilities by inhibiting mTOR activation and downstream glycolysis [6]. Group 3: Broader Research Context - Other studies have linked taurine deficiency to aging and its potential to extend healthspan in various organisms, indicating its multifaceted role in health and disease [9][11]. - Research has shown that taurine supplementation can reactivate exhausted CD8+ T cells, enhancing cancer treatment outcomes, further complicating the narrative around taurine's role in cancer [11]. - The discovery of a novel N-acetyltaurine hydrolase (PTER) suggests new avenues for obesity treatment, indicating taurine's relevance beyond oncology [14].