Rationale for LDH-targeted cancer immunotherapy.

Area of Science:

• Oncology
• Immunology
• Biochemistry

Background:

• Cancer immunotherapies have improved patient survival but face primary and secondary resistance.
• Elevated lactate dehydrogenase (LDH) is a known negative prognostic marker in oncology, often linked to tumor burden.
• Emerging evidence suggests LDH's prognostic value may be independent of tumor burden, impacting immuno-oncology treatment strategies.

Purpose of the Study:

• To review the immunosuppressive effects of lactate dehydrogenase (LDH) on immune cells.
• To explore the potential of LDH-targeted therapies to overcome resistance in cancer immunotherapy.
• To enhance patient survival in immuno-oncology.

Main Methods:

• Literature review of studies investigating lactate dehydrogenase (LDH) in cancer immunotherapy resistance.
• Analysis of the direct immunosuppressive mechanisms of LDH on various immune cell populations.
• Evaluation of preclinical and clinical data on LDH-targeted therapeutic strategies.

Main Results:

• Lactate dehydrogenase (LDH) directly suppresses the function of multiple immune cell types, contributing to an immunosuppressive tumor microenvironment.
• Elevated LDH levels show potential as a predictive biomarker for immunotherapy response, independent of tumor burden.
• Targeting LDH may reverse immune suppression and improve efficacy of existing immunotherapies.

Conclusions:

• Lactate dehydrogenase (LDH) plays a critical role in mediating immune resistance to cancer therapies.
• Targeting LDH presents a promising therapeutic strategy to enhance the effectiveness of cancer immunotherapies.
• Further investigation into LDH-targeted approaches could significantly improve outcomes for cancer patients undergoing immunotherapy.