[Advances in Lactate Metabolic Reprogramming in Non-small Cell Lung Cancer]

Area of Science:

• Oncology
• Cancer Metabolism
• Immunology

Background:

• Non-small cell lung cancer (NSCLC) has high mortality and low survival rates.
• Lactate metabolism is a key feature of NSCLC metabolic reprogramming.
• Lactate influences the tumor microenvironment (TME), immune suppression, metastasis, and chemoresistance.

Purpose of the Study:

• To explore the multifaceted roles of lactate metabolism in NSCLC progression.
• To investigate the link between lactate metabolism, immune evasion, and therapeutic resistance in NSCLC.
• To evaluate the potential of targeting lactate metabolism in combination with immunotherapy for NSCLC treatment.

Main Methods:

• Review of current literature on lactate metabolism in NSCLC.
• Analysis of signaling pathways involved in lactate-mediated effects (e.g., GPR81/PI3K/mTOR).
• Examination of clinical data linking lactate metabolism to NSCLC outcomes and treatment response.

Main Results:

• Lactate accumulation in the TME promotes acidification and energy metabolism.
• The GPR81/PI3K/mTOR pathway links lactate to immune checkpoint molecule expression and immunosuppression.
• Lactate drives epithelial-mesenchymal transition, metastasis, chemoresistance, and relapse via histone lactylation.
• Enhanced lactate metabolism correlates with NSCLC progression and chemotherapy resistance.

Conclusions:

• Targeting lactate metabolism is a promising strategy for NSCLC treatment.
• Combining lactate metabolism inhibition with immunotherapy may yield synergistic antitumor effects.
• Comprehensive inhibition of lactate metabolism and enhancement of antitumor immunity could improve NSCLC precision therapy efficacy.