Lactate generated by cancer cells may be shuttled to the extracellular milieu so that lactate could influence metabolic adaptations by macrophages and microbiotas . Besides the clear role of lactate in the metabolic rewiring of cancer cells and cancer-associated cells such as pro-inflammatory macrophages, there is a clear gap in our understanding of lactate-mediated non-metabolic implications including lactylation form of epigenetic modifications of histones.