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Lactate Metabolism and Immune Modulation in Breast Cancer: A Focused Review on Triple Negative Breast Tumors

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journal contribution
submitted on 2024-06-27, 07:55 and posted on 2024-06-27, 08:18 authored by Adviti Naik, Julie Decock

Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer associated with poor prognosis, early recurrence, and the lack of durable chemotherapy responses and specific targeted treatments. The recent FDA approval for immune checkpoint inhibition in combination with nab-paclitaxel for the treatment of metastatic TNBC created opportunity to advocate for immunotherapy in TNBC patients. However, improving the current low response rates is vital. Most cancers, including TNBC tumors, display metabolic plasticity and undergo reprogramming into highly glycolytic tumors through the Warburg effect. Consequently, accumulation of the metabolic byproduct lactate and extracellular acidification is often observed in several solid tumors, thereby exacerbating tumor cell proliferation, metastasis, and angiogenesis. In this review, we focus on the role of lactate acidosis in the microenvironment of glycolytic breast tumors as a major driver for immune evasion with a special emphasis on TNBCs. In particular, we will discuss the role of lactate regulators such as glucose transporters, lactate dehydrogenases, and lactate transporters in modulating immune functionality and checkpoint expression in numerous immune cell types. This review aims to spark discussion on interventions targeting lactate acidosis in combination with immunotherapy to provide an effective means of improving response to immune checkpoint inhibitors in TNBC, in addition to highlighting challenges that may arise from TNBC tumor heterogeneity.

Other Information

Published in: Frontiers in Oncology
License: https://creativecommons.org/licenses/by/4.0/
See article on publisher's website: https://dx.doi.org/10.3389/fonc.2020.598626


Funding

Open Access funding provided by the Qatar National Library.

Hamad Bin Khalifa University, Qatar Biomedical Research Institute (VR94).

History

Language

  • English

Publisher

Frontiers

Publication Year

  • 2020

License statement

This Item is licensed under the Creative Commons Attribution 4.0 International License.

Institution affiliated with

  • Hamad Bin Khalifa University
  • Qatar Biomedical Research Institute - HBKU
  • Cancer Research Center - QBRI