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Tumour acidosis arises from multiple metabolic processes, including hypoxia-driven glycolysis in poorly vascularized regions, the Warburg effect in well-perfused areas, and carbon dioxide accumulation from tumour respiration. As a sustained ecological stress distinct from physiological pH (\u223c7.4), extracellular acidosis imposes powerful selective pressures within the tumour ecosystem. In response, cancer and stromal cells must adapt through selection of pre-existing phenotypic heterogeneity or acclimate through phenotypic plasticity that enables rapid, non-genetic state transitions. AME influences all stromal components, including fibroblasts, macrophages, extracellular matrix proteins such as collagen and fibronectin, and the broader metabolic habitat, thereby remodelling the tumour niche. Through these adaptive processes, acidosis drives stromal reactivity, niche construction, and reciprocal crosstalk that promote tumour growth, invasion, and metastasis. This review highlights AME as an ecological force governing cancer\u2013stroma symbiosis and proposes mathematical modelling as a systems-level tool to dissect the dynamic and nonlinear interactions that shape the tumour ecosystem and evolution.<\/jats:p>","DOI":"10.1093\/jeb\/voag072","type":"journal-article","created":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T12:51:46Z","timestamp":1787403106000},"source":"Crossref","is-referenced-by-count":0,"title":["Symbiotic cancer cell\u2013stroma crosstalk in the acidic tumour microenvironment"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-8240-0975","authenticated-orcid":false,"given":"Emma R","family":"Downey","sequence":"first","affiliation":[{"name":"Stony Brook Cancer Center, Stony Brook University , Stony Brook ,","place":["United States"]},{"name":"Molecular and Cellular Biology Graduate Program, Stony Brook University , Stony Brook ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana M","family":"Forero\u00a0Pinto","sequence":"additional","affiliation":[{"name":"Integrated Mathematical Oncology Department, H. Lee Moffitt Cancer Center and Research Institute , Tampa ,","place":["United States"]},{"name":"Cancer Biology PhD Program, University of South Florida , Tampa ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail L","family":"Booth","sequence":"additional","affiliation":[{"name":"Stony Brook Cancer Center, Stony Brook University , Stony Brook ,","place":["United States"]},{"name":"Molecular and Cellular Biology Graduate Program, Stony Brook University , Stony Brook ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel","family":"Brown","sequence":"additional","affiliation":[{"name":"Integrated Mathematical Oncology Department, H. 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