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Potential Therapies for Infectious Diseases Based on Targeting Immune Evasion Mechanisms That Pathogens Have in
Jodi Wong1, Stephen Yiu Chuen Choi1,2,3, Rongrong Liu4
1Department of Experimental Therapeutics, BC Cancer Research Centre, Vancouver, BC, Canada.
Abstract:
Many global infectious diseases are not well-controlled, underlining a critical need for new, more effective therapies. Pathogens and pathogen-infected host cells, like cancer cells, evade immune surveillance via immune evasion mechanisms. The present study indicates that pathogenic bacteria, endoparasites, and virus-infected host cells can have immune evasion mechanisms in common with cancers. These include entry into dormancy and metabolic reprogramming to aerobic glycolysis leading to excessive secretion of lactic acid and immobilization of local host immunity. The latter evasion tactic provides a therapeutic target for cancer, as shown by our recent finding that patient-derived cancer xenografts can be growth-arrested, without major host toxicity, by inhibiting their lactic acid secretion (as mediated by the MCT4 transporter)-with evidence of host immunity restoration. Accordingly, the multiplication of bacteria, endoparasites, and viruses that primarily depend on metabolic reprogramming to aerobic glycolysis for survival may be arrested using cancer treatment strategies that inhibit their lactic acid secretion. Immune evasion mechanisms shared by pathogens and cancer cells likely represent fundamental, evolutionarily-conserved mechanisms that may be particularly critical to their welfare. As such, their targeting may lead to novel therapies for infectious diseases.
Insights
New therapies targeting shared immune evasion tactics, like lactic acid secretion, could treat infectious diseases and cancers. Inhibiting lactic acid production may halt pathogen and cancer cell growth while restoring host immunity.
Area of Science:
- Immunology
- Metabolic Reprogramming
- Infectious Diseases
- Oncology
Background:
- Global infectious diseases and cancers pose significant health challenges, often evading immune surveillance through shared mechanisms.
- Pathogens (bacteria, viruses, endoparasites) and cancer cells utilize immune evasion strategies, including dormancy and metabolic reprogramming to aerobic glycolysis.
- Aerobic glycolysis leads to excessive lactic acid secretion, which suppresses local host immunity, a critical factor in disease progression.
Purpose of the Study:
- To investigate common immune evasion mechanisms between pathogens and cancer cells.
- To explore the therapeutic potential of targeting lactic acid secretion as a shared vulnerability.
- To identify novel treatment strategies for both infectious diseases and cancer.
Main Methods:
- Comparative analysis of immune evasion mechanisms in pathogens and cancer cells.
- Investigating the role of aerobic glycolysis and lactic acid secretion (via MCT4 transporter) in immune evasion.
- Evaluating the efficacy of inhibiting lactic acid secretion in patient-derived cancer xenografts.
Main Results:
- Pathogenic microbes and cancer cells share immune evasion tactics, notably metabolic reprogramming to aerobic glycolysis.
- Inhibiting lactic acid secretion in cancer xenografts effectively arrested tumor growth with minimal host toxicity.
- Restoration of host immunity was observed in treated cancer xenografts, suggesting broader therapeutic benefits.
Conclusions:
- Targeting lactic acid secretion, a common metabolic vulnerability, offers a promising therapeutic strategy for both infectious diseases and cancer.
- Shared immune evasion mechanisms between pathogens and cancer cells highlight fundamental biological processes that can be exploited for novel treatments.
- This approach may lead to the development of broadly applicable therapies for a range of debilitating diseases.
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