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Acid affairs in anti-tumour immunity
Federica Cappellesso1,2, Massimiliano Mazzone3,4, Federico Virga5
1Brussels Center for Immunology, Vrije Universiteit Brussel, Brussels, Belgium. Federica.Cappellesso@vub.be.
Cancer Cell International
|October 28, 2024
Summary
Tumor acidity and lactate impair anti-cancer immune responses. Targeting these factors, particularly through monocarboxylate transporters (MCTs), can enhance immunotherapy effectiveness.
Area of Science:
- Oncology
- Immunology
- Metabolism
Background:
- Cancer cells rewire metabolism, leading to an acidic tumor microenvironment (TME) due to lactate accumulation.
- This acidic TME (pH as low as 5.6) disrupts acid-base balance, promoting malignant progression.
- Acidity and lactate negatively impact both innate and adaptive immune cells, hindering anti-tumor responses and reducing immunotherapy efficacy.
Purpose of the Study:
- To review the effects of acidity and lactate on immune cells within the TME.
- To highlight the role of monocarboxylate transporters (MCTs) and other solute carrier transporters (SLCs) in pH regulation and lactate transport.
- To discuss strategies for targeting pH or lactate to improve anti-tumor immunity.
Main Methods:
- Literature review summarizing current knowledge.
- Focus on functional, metabolic, and epigenetic effects of acidity and lactate on immune cells.
- Discussion of transporter roles (MCTs, SLCs) in lactate and bicarbonate exchange.
Main Results:
- Acidity and lactate suppress anti-tumor immune cell function.
- MCTs and SLCs are key players in regulating TME pH and lactate levels.
- Targeting these metabolic factors shows promise for enhancing anti-tumor immunity.
Conclusions:
- Tumor-associated acidity and lactate significantly impair anti-cancer immune responses.
- Monocarboxylate transporters (MCTs) and related SLCs are crucial for managing TME metabolic dysregulation.
- Modulating TME pH and lactate represents a promising therapeutic strategy to boost anti-tumor immunity and immunotherapy outcomes.
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