What is lactate?
Lactate is sort of the conjugate base of the lactic acids that can be used also by the cells as a carbon fuel source.
Some describe it as a waste product from exercise.
Glucose is a sugar molecule that we take in from ice creams and carbohydrates — you know, pasta, rice — and lactate is actually metabolized from glucose.
When you exercise, you produce a lot of lactic acids and then the acidic protons get secreted by the lung and kidney. What remains circulating in the blood is actually the lactate.
What led you to think lactate might have anything to do with cancer?
Initially, our lab was investigating how the tumor acid suppresses the T-cells from attacking the cancer cells. In the process, we used lactate to suppress the process of how the cancer cells convert glucose to lactic acid.
When we performed the study, we found a surprising effect of lactate on the immune cells. Not only is lactate able to inhibit tumor acidity, but it also rejuvenated the tumor-infiltrating T cells, making them more effective at fighting cancer cells.
Do you know at this point exactly how or why that happened?
Tumor cells have many mechanisms to shut down the T cell functions and drive the T cells to exhaustion. What we found is when we introduce high lactate concentrations in the tumor microenvironment, they are able to prevent the T cells from being exhausted, making them, I guess, more effective at killing cancer cells.
Could your findings lead to lactate becoming part of some type of cancer treatment?
We think they could. In the preclinical mouse settings, we found if you combine lactate with the current checkpoint blockade therapy, the tumor vaccines that we created in the lab, or the car-t therapy, in all three different cases we show lactate can significantly improve the antitumor efficacy for the existing cancer immunotherapies.
How far are you away from that actually happening?
This would require clinical testing and I am working with a colleague of mine, Dr. Baran Sumer, who is the head and neck cancer surgeon. We are thinking of testing the hypothesis in the cancer patient populations.
If lactate is a waste product of exercise, is it already helping people who exercise regularly or vigorously?
Hopefully, our study revealed the really surprising immune protective role of lactate that people didn’t know before.
And then, one best way to produce lactate is to exercise. There is much evidence showing exercise can actually help prevent cancer and maybe at least reduce the mortality rates in the patient populations.
And again, it could be a multifactorial effect, but at least our study shows the immune protective effect of lactate. So hopefully people don’t consider this as a waste product and they will get to thinking about the potential benefit of exercising in protecting the immune health.
RESOURCES:
Study: Lactate increases stemness of CD8 + T cells to augment anti-tumor immunity
