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Since lactate acidosis, a hallmark of malignant tissue, was shown to contribute to suppression of effective antitumor immune responses, we investigated the impact of tissue pH and lactate concentration on NK\u2010cell functions in an aggressive model of endogenously arising B\u2010cell lymphoma. The progressive loss of IFN\u2010\u03b3 production by NK cells observed during development of this disease could be ascribed to decreased pH values and lactate accumulation in the microenvironment of growing tumors. Interestingly, IFN\u2010\u03b3 expression by lymphoma\u2010derived NK cells could be restored by transfer of these cells into a normal micromilieu. Likewise, systemic alkalization by oral delivery of bicarbonate to lymphoma\u2010developing mice was capable of enhancing IFN\u2010\u03b3 expression in NK cells and increasing the NK\u2010cell numbers in the lymphoid organs where tumors were growing. By contrast, NK\u2010cell cytotoxicity was dampened<jats:italic>in vivo<\/jats:italic>by tumor\u2010dependent mechanisms that seemed to be different from lactate acidosis and could not be restored in a normal milieu. Most importantly, alkalization and the concomitant IFN\u2010\u03b3 upregulation in NK cells were sufficient to significantly delay tumor growth without any other immunotherapy. This effect was strictly dependent on NK cells.<\/jats:p>","DOI":"10.1002\/ijc.30646","type":"journal-article","created":{"date-parts":[[2017,2,13]],"date-time":"2017-02-13T12:12:42Z","timestamp":1486987962000},"page":"2125-2133","source":"Crossref","is-referenced-by-count":114,"title":["Reversal of tumor acidosis by systemic buffering reactivates NK cells to express IFN\u2010\u03b3 and induces NK cell\u2010dependent lymphoma control without other immunotherapies"],"prefix":"10.1002","volume":"140","author":[{"given":"Johann","family":"P\u00f6tzl","sequence":"first","affiliation":[{"name":"Institut f\u00fcr Molekulare Immunologie, Helmholtz\u2010Zentrum M\u00fcnchen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Roser","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Molekulare Immunologie, Helmholtz\u2010Zentrum M\u00fcnchen Germany"},{"name":"AG Translationale Molekulare Immunologie, Helmholtz\u2010Zentrum M\u00fcnchen 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