Subscribe to Journal
Get full journal access for 1 year
only $41.58 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Chouaib S, Noman MZ, Kosmatopoulos K, Curran MA. Hypoxic stress: obstacles and opportunities for innovative immunotherapy of cancer. Oncogene. 2017;36:439–45. https://doi.org/10.1038/onc.2016.225.
Lazarus D, Peters C, Stockmann A, Eliasof S, Jayaraman L. Abstract 3209: CRLX101, an investigational nanoparticle-drug conjugate of camptothecin, demonstrates synergy with immunotherapy agents in preclinical models. Cancer Res. 2016;76:3209.
McDonald PC, Chafe SC, Dedhar S. Overcoming hypoxia-mediated tumor progression: combinatorial approaches targeting pH regulation, angiogenesis and immune dysfunction. Front Cell Dev Biol. 2016;4:27.
Lardner A. The effects of extracellular pH on immune function. J Leukoc Biol. 2001;69:522–30.
El-Kenawi A, Gatenbee C, Robertson-Tessi M, Bravo R, Dhillon J, Balagurunathan Y, et al. Acidity promotes tumour progression by altering macrophage phenotype in prostate cancer. Br J Cancer. 2019;121:556–66.
Horsman MR, Mortensen LS, Petersen JB, Busk M, Overgaard J. Imaging hypoxia to improve radiotherapy outcome. Nat Rev Clin Oncol. 2012;9:674–87. https://doi.org/10.1038/nrclinonc.2012.171.
Zhang X, Lin Y, Gillies RJ. Tumor pH and its measurement. J Nucl Med. 2010;51:1167–70. https://doi.org/10.2967/jnumed.109.068981.
Wilson WR, Hay MP. Targeting hypoxia in cancer therapy. Nat Rev Cancer. 2011;11:393–410. https://doi.org/10.1038/nrc3064.
Lindner LH. Hypoxia-activated prodrug: an appealing preclinical concept yet lost in clinical translation. Lancet Oncol. 2017;18:991–3. https://doi.org/10.1016/S1470-2045(17)30401-1.
Jindal V. Immunotherapy: a glimmer of hope for metastatic prostate cancer. Chin Clin Oncol. 2018;7:61. https://doi.org/10.21037/cco.2018.02.01.
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. https://doi.org/10.1158/0008-5472.CAN-15-1743.
Wong WY, DeLuca CI, Tian B, Wilson I, Molund S, Warriar N, et al. Urease-induced alkalinization of extracellular pH and its antitumor activity in human breast and lung cancers. J Exp Ther Oncol. 2005;5:93–99.
Damgaci S, Ibrahim-Hashim A, Enriquez-Navas PM, Pilon-Thomas S, Guvenis A, Gillies RJ. Hypoxia and acidosis: immune suppressors and therapeutic targets. Immunology. 2018;154:354–62.
Doherty JR, Cleveland JL. Targeting lactate metabolism for cancer therapeutics. J Clin Investig. 2013;123:3685–92.
This article is published as part of a supplement sponsored by NuOmix-Research k.s. The conference was financially supported by Protina Pharmazeutische GmbH, Germany and Sirius Pharma, Germany, and organized by NuOmix-Research k.s. Neither company had any role in writing of the paper.
Conflict of interest
SD and AI-H received grant support from Helix Biopharma. RJG received grant support from Helix Biopharma & Healthmyne, and NIH Small Business Innovation Research (SBIR) with Healthmyne, Inc; RJG also holds stock HealthMyne, Inc (H-M), which is a commercial quantitative PACS system for reading and analysis of radiographic scans, and held stock in Helix until 2017. SP-T received grant support from the American Cancer Society.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Damgaci, S., Enriquez-Navas, P.M., Pilon-Thomas, S. et al. Immunotherapy on acid: opportunities and challenges. Eur J Clin Nutr 74, 3–6 (2020). https://doi.org/10.1038/s41430-020-0683-7