This work is licensed under the Creative Commons Attribution 4.0 International License.
Dvorak HF, Weaver VM, Tlsty TD, Bergers G. Tumor microenvironment and progression. J Surg Oncol. 2011; 103:468–74.DvorakHFWeaverVMTlstyTDBergersGTumor microenvironment and progressionJ Surg Oncol201110346874Search in Google Scholar
Apostolova P, Pearce EL. Lactic acid and lactate: revisiting the physiological roles in the tumor microenvironment. Trends Immunol. 2022; 43:969–77.ApostolovaPPearceELLactic acid and lactate: revisiting the physiological roles in the tumor microenvironmentTrends Immunol20224396977Search in Google Scholar
Dhup S, Dadhich RK, Porporato PE, Sonveaux P. Multiple biological activities of lactic acid in cancer: influences on tumor growth, angiogenesis and metastasis. Curr Pharma Des. 2012; 18:1319–30.DhupSDadhichRKPorporatoPESonveauxPMultiple biological activities of lactic acid in cancer: influences on tumor growth, angiogenesis and metastasisCurr Pharma Des201218131930Search in Google Scholar
Cardone RA, Alfarouk KO, Elliott RL, Alqahtani SS, Ahmed SBM, Aljarbou AN, et al. The role of sodium hydrogen exchanger 1 in dysregulation of proton dynamics and reprogramming of cancer metabolism as a sequela. Int J Mol Sci. 2019; 20:3694. doi: 10.3390/ijms20153694CardoneRAAlfaroukKOElliottRLAlqahtaniSSAhmedSBMAljarbouANThe role of sodium hydrogen exchanger 1 in dysregulation of proton dynamics and reprogramming of cancer metabolism as a sequelaInt J Mol Sci201920369410.3390/ijms20153694Open DOISearch in Google Scholar
Gaohua L, Miao X, Dou L. Crosstalk of physiological pH and chemical pKa under the umbrella of physiologically based pharmacokinetic modeling of drug absorption, distribution, metabolism, excretion, and toxicity. Expert Opin Drug Metab Toxicol. 2021; 17:1103–24.GaohuaLMiaoXDouLCrosstalk of physiological pH and chemical pKa under the umbrella of physiologically based pharmacokinetic modeling of drug absorption, distribution, metabolism, excretion, and toxicityExpert Opin Drug Metab Toxicol202117110324Search in Google Scholar
Feng L, Xie R, Wang C, Gai S, He F, Yang D, et al. Magnetic targeting, tumor microenvironment-responsive intelligent nanocatalysts for enhanced tumor ablation. ACS Nano. 2018; 12:11000–12.FengLXieRWangCGaiSHeFYangDMagnetic targeting, tumor microenvironment-responsive intelligent nanocatalysts for enhanced tumor ablationACS Nano2018121100012Search in Google Scholar
Swietach P, Vaughan-Jones RD, Harris AL, Hulikova A. The chemistry, physiology and pathology of pH in cancer. Philos Trans R Soc Lond B Biol Sci. 2014; 369:20130099. doi: 10.1098/rstb.2013.0099SwietachPVaughan-JonesRDHarrisALHulikovaAThe chemistry, physiology and pathology of pH in cancerPhilos Trans R Soc Lond B Biol Sci20143692013009910.1098/rstb.2013.0099Open DOISearch in Google Scholar
Veatch JR, Lee SM, Shasha C, Singhi N, Szeto JL, Moshiri AS, et al. Neoantigen-specific CD4+ T cells in human melanoma have diverse differentiation states and correlate with CD8+ T cell, macrophage, and B cell function. Cancer Cell. 2022; 40:393–409.e9.VeatchJRLeeSMShashaCSinghiNSzetoJLMoshiriASNeoantigen-specific CD4+ T cells in human melanoma have diverse differentiation states and correlate with CD8+ T cell, macrophage, and B cell functionCancer Cell202240393409.e9Search in Google Scholar
Kim R. Cancer immunoediting: from immune surveillance to immune escape. Cancer Immunother. 2007; 1:9–27.KimRCancer immunoediting: from immune surveillance to immune escapeCancer Immunother20071927Search in Google Scholar
Gajewski TF, Schreiber H, Fu YX. Innate and adaptive immune cells in the tumor microenvironment. Nat Immunol. 2013; 14:1014–22.GajewskiTFSchreiberHFuYXInnate and adaptive immune cells in the tumor microenvironmentNat Immunol201314101422Search in Google Scholar
Kitamura T, Qian BZ, Pollard JW. Immune cell promotion of metastasis. Nat Rev Immunol. 2015; 15:73–86.KitamuraTQianBZPollardJWImmune cell promotion of metastasisNat Rev Immunol2015157386Search in Google Scholar
Finn OJ. Immuno-oncology: understanding the function and dysfunction of the immune system in cancer. Ann Oncol. 2012; 23:viii6–9.FinnOJImmuno-oncology: understanding the function and dysfunction of the immune system in cancerAnn Oncol201223viii69Search in Google Scholar
Hao NB, Lü MH, Fan YH, Cao YL, Zhang ZR, Yang SM. Macrophages in tumor microenvironments and the progression of tumors. Clin Dev Immunol. 2012; 2012:948098. doi: 10.1155/2012/948098HaoNBLüMHFanYHCaoYLZhangZRYangSMMacrophages in tumor microenvironments and the progression of tumorsClin Dev Immunol2012201294809810.1155/2012/948098Open DOISearch in Google Scholar
Korkaya H, Liu S, Wicha MS. Breast cancer stem cells, cytokine networks, and the tumor microenvironment. J Clin Invest. 2011; 121:3804–9.KorkayaHLiuSWichaMSBreast cancer stem cells, cytokine networks, and the tumor microenvironmentJ Clin Invest201112138049Search in Google Scholar
Salmon H, Donnadieu E. Within tumors, interactions between T cells and tumor cells are impeded by the extracellular matrix. Oncoimmunology. 2012; 1:992–4.SalmonHDonnadieuEWithin tumors, interactions between T cells and tumor cells are impeded by the extracellular matrixOncoimmunology201219924Search in Google Scholar
Le Page C, Marineau A, Bonza PK, Rahimi K, Cyr L, Labouba I, et al. BTN3A2 expression in epithelial ovarian cancer is associated with higher tumor infiltrating T cells and a better prognosis. PLoS One. 2012; 7:e38541. doi: 10.1371/journal.pone.0038541Le PageCMarineauABonzaPKRahimiKCyrLLaboubaIBTN3A2 expression in epithelial ovarian cancer is associated with higher tumor infiltrating T cells and a better prognosisPLoS One20127e3854110.1371/journal.pone.0038541Open DOISearch in Google Scholar
Shaban M, Raza SEA, Hassan M, Jamshed A, Mushtaq S, Loya A, et al. A digital score of tumour-associated stroma infiltrating lymphocytes predicts survival in head and neck squamous cell carcinoma. J Pathol. 2022; 256:174–85.ShabanMRazaSEAHassanMJamshedAMushtaqSLoyaAA digital score of tumour-associated stroma infiltrating lymphocytes predicts survival in head and neck squamous cell carcinomaJ Pathol202225617485Search in Google Scholar
Kak G, Raza M, Tiwari BK. Interferon-gamma (IFN-γ): exploring its implications in infectious diseases. Biomol Concepts. 2018; 9:64–79.KakGRazaMTiwariBKInterferon-gamma (IFN-γ): exploring its implications in infectious diseasesBiomol Concepts201896479Search in Google Scholar
Jorgovanovic D, Song M, Wang L, Zhang Y. Roles of IFN-γ in tumor progression and regression: a review. Biomark Res. 2020; 8:49. doi: 10.1186/s40364-020-00228-xJorgovanovicDSongMWangLZhangYRoles of IFN-γ in tumor progression and regression: a reviewBiomark Res202084910.1186/s40364-020-00228-xOpen DOISearch in Google Scholar
Beatty GL, Paterson Y. IFN-γ-dependent inhibition of tumor angiogenesis by tumor-infiltrating CD4+ T cells requires tumor responsiveness to IFN-γ. J Immunol. 2001; 166:2276–82.BeattyGLPatersonYIFN-γ-dependent inhibition of tumor angiogenesis by tumor-infiltrating CD4+ T cells requires tumor responsiveness to IFN-γJ Immunol2001166227682Search in Google Scholar
Nakahira M, Ahn HJ, Park WR, Gao P, Tomura M, Park CS, et al. Synergy of IL-12 and IL-18 for IFN-γ gene expression: IL-12-induced STAT4 contributes to IFN-γ promoter activation by up-regulating the binding activity of IL-18-induced activator protein 1. J Immunol. 2002; 168:1146–53.NakahiraMAhnHJParkWRGaoPTomuraMParkCSSynergy of IL-12 and IL-18 for IFN-γ gene expression: IL-12-induced STAT4 contributes to IFN-γ promoter activation by up-regulating the binding activity of IL-18-induced activator protein 1J Immunol2002168114653Search in Google Scholar
Micallef MJ, Yoshida K, Kawai S, Hanaya T, Kohno K, Arai S, et al. In vivo antitumor effects of murine interfero-γ-inducing factor/interleukin-18 in mice bearing syngeneic Meth A sarcoma malignant ascites. Cancer Immunol Immunother. 1997; 43:361–7.MicallefMJYoshidaKKawaiSHanayaTKohnoKAraiSIn vivo antitumor effects of murine interfero-γ-inducing factor/interleukin-18 in mice bearing syngeneic Meth A sarcoma malignant ascitesCancer Immunol Immunother1997433617Search in Google Scholar
McAllister SS, Weinberg RA. The tumour-induced systemic environment as a critical regulator of cancer progression and metastasis. Nat Cell Biol. 2014; 16:717–27.McAllisterSSWeinbergRAThe tumour-induced systemic environment as a critical regulator of cancer progression and metastasisNat Cell Biol20141671727Search in Google Scholar
Som A, Bloch S, Ippolito JE, Achilefu S. Acidic extracellular pH of tumors induces octamer-binding transcription factor 4 expression in murine fibroblasts in vitro and in vivo. Sci Rep. 2016; 6:27803. doi: 10.1038/srep27803SomABlochSIppolitoJEAchilefuSAcidic extracellular pH of tumors induces octamer-binding transcription factor 4 expression in murine fibroblasts in vitro and in vivoSci Rep201662780310.1038/srep27803Open DOISearch in Google Scholar
Avnet S, Di Pompo G, Chano T, Errani C, Ibrahim-Hashim A, Gillies RJ, et al. Cancer-associated mesenchymal stroma fosters the stemness of osteosarcoma cells in response to intratumoral acidosis via NF-kB activation. Int J Cancer. 2017; 140:1331–45.AvnetSDi PompoGChanoTErraniCIbrahim-HashimAGilliesRJCancer-associated mesenchymal stroma fosters the stemness of osteosarcoma cells in response to intratumoral acidosis via NF-kB activationInt J Cancer2017140133145Search in Google Scholar
Park EK, Jung HS, Yang HI, Yoo MC, Kim C, Kim KS. Optimized THP-1 differentiation is required for the detection of responses to weak stimuli. Inflamm Res. 2007; 56:45–50.ParkEKJungHSYangHIYooMCKimCKimKSOptimized THP-1 differentiation is required for the detection of responses to weak stimuliInflamm Res2007564550Search in Google Scholar
Shelke GV, Lässer C, Gho YS, Lötvall J. Importance of exosome depletion protocols to eliminate functional and RNA-containing extracellular vesicles from fetal bovine serum. J Extracell Vesicles. 2014; 3:24783. doi: 10.3402/jev.v3.24783ShelkeGVLässerCGhoYSLötvallJImportance of exosome depletion protocols to eliminate functional and RNA-containing extracellular vesicles from fetal bovine serumJ Extracell Vesicles201432478310.3402/jev.v3.24783Open DOISearch in Google Scholar
Park HJ, Lyons JC, Ohtsubo T, Song CW. Acidic environment causes apoptosis by increasing caspase activity. Br J Cancer. 1999; 80:1892–7.ParkHJLyonsJCOhtsuboTSongCWAcidic environment causes apoptosis by increasing caspase activityBr J Cancer19998018927Search in Google Scholar
Sharma V, Kaur R, Bhatnagar A, Kaur J. Low-pH-induced apoptosis: role of endoplasmic reticulum stress-induced calcium permeability and mitochondria-dependent signaling. Cell Stress Chaperones. 2015; 20:431–40.SharmaVKaurRBhatnagarAKaurJLow-pH-induced apoptosis: role of endoplasmic reticulum stress-induced calcium permeability and mitochondria-dependent signalingCell Stress Chaperones20152043140Search in Google Scholar
Wang M, Zhao J, Zhang L, Wei F, Lian Y, Wu Y, et al. Role of tumor microenvironment in tumorigenesis. J Cancer. 2017; 8:761–73.WangMZhaoJZhangLWeiFLianYWuYRole of tumor microenvironment in tumorigenesisJ Cancer2017876173Search in Google Scholar
Lardner A. The effects of extracellular pH on immune function. J Leukoc Biol. 2001; 69:522–30.LardnerAThe effects of extracellular pH on immune functionJ Leukoc Biol20016952230Search in Google Scholar
Kellum JA. Metabolic acidosis in patients with sepsis: epiphenomenon or part of the pathophysiology? Crit Care Resusc. 2004; 6:197–203.KellumJAMetabolic acidosis in patients with sepsis: epiphenomenon or part of the pathophysiology?Crit Care Resusc20046197203Search in Google Scholar
Li H, Fan X, Houghton J. Tumor microenvironment: the role of the tumor stroma in cancer. J Cell Biochem. 2007; 101:805–15.LiHFanXHoughtonJTumor microenvironment: the role of the tumor stroma in cancerJ Cell Biochem200710180515Search in Google Scholar
Cai G, Kastelein RA, Hunter CA. IL-10 enhances NK cell proliferation, cytotoxicity and production of IFN-γ when combined with IL-18. Eur J Immunol. 1999; 29:2658–65.CaiGKasteleinRAHunterCAIL-10 enhances NK cell proliferation, cytotoxicity and production of IFN-γ when combined with IL-18Eur J Immunol199929265865Search in Google Scholar
Kojima H, Aizawa Y, Yanai Y, Nagaoka K, Takeuchi M, Ohta T, et al. An essential role for NF-κB in IL-18-induced IFN-γ expression in KG-1 cells. J Immunol. 1999; 162:5063–9.KojimaHAizawaYYanaiYNagaokaKTakeuchiMOhtaTAn essential role for NF-κB in IL-18-induced IFN-γ expression in KG-1 cellsJ Immunol199916250639Search in Google Scholar
Luciani F, Spada M, De Milito A, Molinari A, Rivoltini L, Montinaro A, et al. Effect of proton pump inhibitor pretreatment on resistance of solid tumors to cytotoxic drugs. J Natl Cancer Inst. 2004; 96:1702–13.LucianiFSpadaMDe MilitoAMolinariARivoltiniLMontinaroAEffect of proton pump inhibitor pretreatment on resistance of solid tumors to cytotoxic drugsJ Natl Cancer Inst200496170213Search in Google Scholar
Lu ZN, Shi ZY, Dang YF, Cheng YN, Guan YH, Hao ZJ, et al. Pantoprazole pretreatment elevates sensitivity to vincristine in drug-resistant oral epidermoid carcinoma in vitro and in vivo. Biomed Pharmacother. 2019; 120:109478. doi: 10.1016/j.biopha.2019.109478.LuZNShiZYDangYFChengYNGuanYHHaoZJPantoprazole pretreatment elevates sensitivity to vincristine in drug-resistant oral epidermoid carcinoma in vitro and in vivoBiomed Pharmacother201912010947810.1016/j.biopha.2019.109478Open DOISearch in Google Scholar
Ferrari S, Perut F, Fagioli F, Brach Del Prever A, Meazza C, Parafioriti A, et al. Proton pump inhibitor chemosensitization in human osteosarcoma: from the bench to the patients’ bed. J Transl Med. 2013; 11:268. doi: 10.1186/1479-5876-11-268FerrariSPerutFFagioliFBrach Del PreverAMeazzaCParafioritiAProton pump inhibitor chemosensitization in human osteosarcoma: from the bench to the patients’ bedJ Transl Med20131126810.1186/1479-5876-11-268Open DOISearch in Google Scholar
Matsumura S, Ishikawa T, Yoshida J, Morita R, Sakakida T, Endo Y, et al. Proton pump inhibitors enhance the antitumor effect of chemotherapy for esophageal squamous cell carcinoma. Cancers (Basel). 2022; 14:2395. doi: 10.3390/cancers14102395MatsumuraSIshikawaTYoshidaJMoritaRSakakidaTEndoYProton pump inhibitors enhance the antitumor effect of chemotherapy for esophageal squamous cell carcinomaCancers (Basel)202214239510.3390/cancers14102395Open DOISearch in Google Scholar
Wang JX, Choi SYC, Niu X, Kang N, Xue H, Killam J, Wang Y. Lactic acid and an acidic tumor microenvironment suppress anticancer immunity. Int J Mol Sci. 2020; 21:8363. doi: 10.3390/ijms21218363WangJXChoiSYCNiuXKangNXueHKillamJWangYLactic acid and an acidic tumor microenvironment suppress anticancer immunityInt J Mol Sci202021836310.3390/ijms21218363Open DOISearch in Google Scholar
Fischer K, Hoffmann P, Voelkl S, Meidenbauer N, Ammer J, Edinger M, et al. Inhibitory effect of tumor cell-derived lactic acid on human T cells. Blood. 2007; 109:3812–9.FischerKHoffmannPVoelklSMeidenbauerNAmmerJEdingerMInhibitory effect of tumor cell-derived lactic acid on human T cellsBlood200710938129Search in Google Scholar
Fischer B, Müller B, Fischer KG, Baur N, Kreutz W. Acidic pH inhibits non-MHC-restricted killer cell functions. Clin Immunol. 2000; 96:252–63.FischerBMüllerBFischerKGBaurNKreutzWAcidic pH inhibits non-MHC-restricted killer cell functionsClin Immunol20009625263Search in Google Scholar
Müller B, Fischer B, Kreutz W. An acidic microenvironment impairs the generation of non-major histocompatibility complex-restricted killer cells. Immunology. 2000; 99:375–84.MüllerBFischerBKreutzWAn acidic microenvironment impairs the generation of non-major histocompatibility complex-restricted killer cellsImmunology20009937584Search in Google Scholar
Kano A. Tumor cell secretion of soluble factor(s) for specific immunosuppression. Sci Rep. 2015; 5:8913. doi: 10.1038/srep08913KanoATumor cell secretion of soluble factor(s) for specific immunosuppressionSci Rep20155891310.1038/srep08913Open DOISearch in Google Scholar
Sun X, Zhang J, Zhao X, Yang C, Shi M, Zhang B, et al. Binary regulation of the tumor microenvironment by a pH-responsive reversible shielding nanoplatform for improved tumor chemoimmunotherapy. Acta Biomater. 2022; 138:505–17.SunXZhangJZhaoXYangCShiMZhangBBinary regulation of the tumor microenvironment by a pH-responsive reversible shielding nanoplatform for improved tumor chemoimmunotherapyActa Biomater202213850517Search in Google Scholar
Bellone M, Calcinotto A, Filipazzi P, De Milito A, Fais S, Rivoltini L. The acidity of the tumor microenvironment is a mechanism of immune escape that can be overcome by proton pump inhibitors. Oncoimmunology. 2013; 2:e22058. doi: 10.4161/onci.22058BelloneMCalcinottoAFilipazziPDe MilitoAFaisSRivoltiniLThe acidity of the tumor microenvironment is a mechanism of immune escape that can be overcome by proton pump inhibitorsOncoimmunology20132e2205810.4161/onci.22058Open DOISearch in Google Scholar
Pilon-Thomas S, Kodumudi KN, El-Kenawi AE, Russell S, Weber AM, Luddy K, et al. Neutralization of tumor acidity improves antitumor responses to immunotherapy. Cancer Res. 2016; 76:1381–90.Pilon-ThomasSKodumudiKNEl-KenawiAERussellSWeberAMLuddyKNeutralization of tumor acidity improves antitumor responses to immunotherapyCancer Res201676138190Search in Google Scholar
Calcinotto A, Filipazzi P, Grioni M, Iero M, De Milito A, Ricupito A, et al. Modulation of microenvironment acidity reverses anergy in human and murine tumor-infiltrating T lymphocytespH and T-cell anergy. Cancer Res. 2012; 72:2746–56.CalcinottoAFilipazziPGrioniMIeroMDe MilitoARicupitoAModulation of microenvironment acidity reverses anergy in human and murine tumor-infiltrating T lymphocytespH and T-cell anergyCancer Res201272274656Search in Google Scholar