Targeting tumor-associated acidity in cancer immunotherapy

Area of Science:

• Immunology and Oncology
• Cancer Biology

Background:

• Checkpoint inhibitors like CTLA-4 and PD-1 antibodies have revolutionized cancer therapy for several malignancies.
• Limited patient response to checkpoint blockade highlights the need to understand resistance mechanisms.
• Tumor microenvironment factors, particularly acidity, are implicated in limiting immunotherapy efficacy.

Purpose of the Study:

• To review the impact of tumor-associated acidity on T cell-mediated cancer immunotherapy.
• To explore mechanisms by which acidity inhibits T cell function in the tumor microenvironment.
• To discuss potential strategies for overcoming acidity-induced resistance to immunotherapies.

Main Methods:

• Review of existing literature on checkpoint inhibitors, tumor microenvironment, and cancer acidity.
• Analysis of lactate dehydrogenase as a marker for tumor acidity and immunotherapy response.
• Discussion of T cell function inhibition within acidic tumor environments.

Main Results:

• Checkpoint inhibitors have transformed treatment for melanoma, renal cell carcinoma, lung, Hodgkin lymphoma, and bladder cancers.
• Serum lactate dehydrogenase activity correlates with tumor acidity and predicts response to checkpoint inhibition.
• Tumor acidity is a significant barrier to T cell function and immunotherapy effectiveness.

Conclusions:

• Tumor-associated acidity represents a critical challenge for T cell-mediated cancer immunotherapy.
• Understanding and targeting acidity is essential for improving patient outcomes with checkpoint inhibitors.
• Developing strategies to mitigate tumor acidity may enhance the efficacy of current and future immunotherapies.