Lactate’s Potential is an Immunotherapy Supplement for Cancer Treatments

The research team from the Dallas-based UT Southwestern Simmons Cancer Center reported that lactate, a metabolic by-product produced by cells during strenuous exercise, may rejuvenate immune cells that fight cancer. The study, “Lactate increases stemness of CD8 + T cells to augment anti-tumor immunity,” was published in Nature Communications on September 6.

The corresponding author of the study, Jinming Gao, Ph.D., professor of cell biology, otolaryngology-head and neck surgery, and pharmacology, highlighted their discovery “to recognize the role of a waste product in fighting cancer.” According to the scientists, the findings provided fresh insight to develop new strategies to amplify the anti-tumor effect of cancer immunotherapies.  

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An Attempt to Clear Up Lactate’s Role in the Body

Lactate is a key metabolite produced from the glycolytic metabolism of glucose molecules, yet it also serves as a primary carbon fuel source for many cell types. While in the case of the tumor-immune microenvironment, the effect of lactate on cancer and immune cells could be rather complicated and hard to distinguish, as it may be further confounded by acidic protons, a co-product of glycolysis. 

The role of lactate has long been discussed since the discovery of the Warburg effect(a preferential production of lactate even in aerobic conditions) nearly a century ago. The metabolic waste then became the new target of scientists while more and more diverse functions such as immunosuppression on glycolytic tumors or overtaking glucose as a primary carbon fuel source for a majority of tissues, including immune organs. However, the effect of lactate on CD8+ T cell immune functions is not well understood with immune suppressive functions reported for lactic acid in glycolytic tumors. Thus, the team decided to focus on clarifying the role of lactate in the tumor microenvironment.

Metabolic Reprogramming as a New Target of Scientists

Researchers gave lactate injections to mice with colon cancer or melanoma during the study, while the control received glucose injections. Surprisingly, mice treated with lactate experienced significant tumor reductions, while glucose injections had little suppressive effects. Researchers repeated the experiment in mice genetically engineered to lack T cells. This anti-tumor benefit was blocked, suggesting that the T cell population correlates to the tumor-suppressing effect of lactate.  

Author

Nai Ye Yeat