Lactic acid enhances cancer immunotherapy? Experts reveal the truth! Is the tumor microenvironment the key?
Can lactic acid increase the effectiveness of immunotherapy? Experts: More evidence is needed
The lactic acid produced by the human body after exercise is generally considered a metabolic waste, but may it be helpful in tumor immunotherapy? A study published in Nature Communications claimed that lactic acid can increase the stem cell properties of CD8+ cytotoxic T cells and increase anti-tumor immunity.
After the researchers treated mice with sodium lactate, one tumor model found that lactate increased TCF-1 expression and reduced CD8 + T cell apoptosis, and another model showed that lactate increased an anti-PD-1 immunotherapy effect. The research team claimed that various models show that lactic acid can enhance the effect of tumor immunotherapy, including immune checkpoint inhibitors, cancer vaccines and CAR-T immune cell therapy.
Can lactic acid really enhance cancer immunotherapy? Li Yuelun, a researcher at the Cancer Institute of the National Institutes of Health and director of the Mitochondrial and Immuno-Tumor Microenvironment Laboratory, was interviewed by “healthorn” and asked whether the “sodium lactate” used in this study is equivalent to the endogenous lactic acid in the human body. Unable to confirm; is the high concentration of lactic acid used in the mouse model applicable to humans? Previous literature has pointed out that lactic acid produced in the tumor microenvironment is related to the suppression of immune cells and may be an indicator of the impact of the immune mechanism. . Therefore, the conclusions of this study must be viewed with caution and more further clinical studies are awaited.
What is the relationship between lactic acid and cancer immunotherapy?
Li Yuelun said that during the rapid growth of tumors, various tissues are in a hypoxic microenvironment. The way cancer cells metabolize energy does not use the citric acid cycle (TCA cycle) but uses faster glycolysis (Glycolysis) to penetrate Glucose is decomposed into lactic acid by enzymes, and then secreted into surrounding tissues as a carbon source for cancer cell growth to support cancer growth. After tumor cells grow rapidly, a large amount of lactic acid produced by metabolizing glucose will enter the tumor microenvironment, where glucose The process of converting glucose into ATP is less efficient, so cancer cells require larger amounts of glucose.
The so-called “tumor microenvironment” does not only exist in cancer cells, but also includes stromal cells, vascular cells, immune cells, etc. The normal functions of immune cells are more likely to be inhibited in an acidic environment. Li Yuelun pointed out that past literature found that lactic acid is mostly related to the suppression of immune cells in tumor treatment. For example, a paper published in “Cancer Cell” last year focused on PD-1 research and found that lactic acid can stimulate the increase of PD-1, causing immune suppression and reducing the activity of immune cells, making it more likely to promote the occurrence of cancer. Therefore, more research evidence is needed to prove whether lactic acid treatment can really increase the number of T cells and help the effect of immunotherapy.
Immunotherapy methods and treatment response rate bottlenecks?
Immunotherapy is considered an important hope in treating cancer, and more and more research is being devoted to related issues. Li Yuelun explained that the main function of immunotherapy is to eliminate cancer cells by increasing one’s own immunity. Currently, there are two main methods of immunotherapy. One is monoclonal antibodies that inhibit PD-L1. This is an immune checkpoint inhibitor therapy that allows the immune system to correctly identify cancer cells and exert anti-cancer effects.
The other is immune cell therapy, which arms and strengthens immune cells to effectively execute immune responses, such as CAR-T and CAR-NK, which means reintroducing armed and trained immune cells (T cells, NK cells) into the body to achieve enhancement. Immunity effects.
Li Yuelun pointed out that immunotherapy is a major progress in cancer treatment, but the bottleneck of treatment response rate needs to be broken. For example, some patients have high expression of PD-L1, but the treatment effect is still not as good as expected. In addition, immunotherapy has inconsistent effects on “blood cancers” and “solid tumors”. Immunotherapy is more effective for blood-related cancers such as leukemia. However, it is less effective for solid cancers such as colorectal cancer, breast cancer, and lung cancer. It is only about 20-30% effective. Immunotherapy alone is often not ideal.
The key to the effectiveness of immunotherapy lies in the tumor microenvironment?
The key to improving the effect of immunotherapy may lie in the “tumor microenvironment”? Li Yuelun said that if the immune status of the tumor microenvironment is not good, it will be difficult to achieve effective immune activation using immunotherapy. Usually the unfavorable environment of immunosuppression is called cold tumor (cold tumor), and the activated immune environment is called hot tumor (hot tumor). To properly deal with the threat of cancer, it is necessary to comprehensively understand the tumor microenvironment of cancer cells and plan “personalized precision medicine” from individual differences, immune status, cancer cell composition or genetic changes.
Li Yuelun said that scientists are currently trying to find more effective methods to evaluate immunotherapy, such as using the “organoid model” to remove cancer cells and culture them to test the efficacy; there are also scholars in Taiwan using intestinal bacteria to evaluate prospective studies on immunotherapy for liver cancer. In the face of cancer, combination therapy based on immunotherapy and combined with other therapies is expected to achieve better results in the future.
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