ArticleFrontiers in oncology2025
The CILLO-E Hypothesis: Erythrocyte-Driven Acidosis and Early Eryptosis as Drivers of Cancer-Associated Anemia.
Article in Frontiers in oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: The tumor microenvironment (TME) is characterized by high lactate and proton accumulation resulting from glycolytic metabolism. While acidosis is known to influence immune and stromal cells, its direct effects on erythrocytes-the most abundant circulating cells-remain underexplored. Methods: An integrative review of cancer metabolism, erythrocyte physiology, and lactate transport systems was conducted using PubMed and Web of Science. From this synthesis, the CILLO-E hypothesis (Cancer-Induced Lactate Load on Erythrocytes) was formulated. Results: The hypothesis proposes that lactate and protons enter erythrocytes via MCT1, leading to intracellular acidification. This process disrupts glycolytic enzymes, reduces ATP production, and impairs Na Conclusions: The CILLO-E hypothesis reframes erythrocytes as active metabolic targets in the TME rather than passive oxygen carriers. By linking lactate-driven metabolic stress to erythrocyte dysfunction, anemia, and systemic hypoxia, it suggests a feedback loop that promotes tumor progression and highlights opportunities for erythrocyte-based biomarkers and therapeutic strategies.
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