Lactate and Lactylation: Dual Regulators of T-Cell-Mediated Tumor Immunity and Immunotherapy

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

In this interesting review, the Authors evaluate the role of lactate and lactylation processes in the immune response, with the main focus set on the cancer immunotherapy. First, the modifications of metabolism of the T cell subsets (e.g. effector, regulatory, memory, naïve) in the tumor microenvironment are analyzed. Then, the functions of histone and non-histone lactylation in the immune responses and in the tumor immune evasion processes are discussed. The Authors have explored the mechanisms of immune stimulation and suppression of the influence of lactate and lactylation. Several examples of the lactate and lactylation inhibitors have been  presented. The utilization of different drugs targeting lactate metabolism during the cancer treatment was also studied. In summary, the future perspectives have been highlighted.

I recommend the paper for publication after minor revision addressing the issues listed below.

1.      For the benefit of general Readership, the abbreviations should be defined at their first use, e.g. CIRI, YY1, T-bet, MOESIN, HDAC, PCa.

2.      The names of enzymes and chemicals should be written in lowercase (e.g. Granzyme B, diclofenac).

3.      The chemical formula of calcium ion is incorrect. Please correct appropriately.

4.      In Figure 3, the term “Glucolysis” should be “Glycolysis”. Please correct appropriately.

Author Response

Please see the attachment. 

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

The review article titled "Lactate and lactylation: Dual regulators in T cell-mediated tumor immunity and immunotherapy" by Hao and colleagues provides a comprehensive review of lactylation as a post-translational modification of histone and non-histone proteins and its impact on T-cell differentiation and function in the tumor microenvironment as well as impact on therapeutic response. The manuscript is well written and organized. 

Author Response

Reviewer#2

Comment:

The review article titled "Lactate and lactylation: Dual regulators in T cell-mediated tumor immunity and immunotherapy" by Hao and colleagues provides a comprehensive review of lactylation as a post-translational modification of histone and non-histone proteins and its impact on T-cell differentiation and function in the tumor microenvironment as well as impact on therapeutic response. The manuscript is well written and organized. 

Response: We greatly appreciate the time and effort you dedicated to reviewing our work, and we sincerely thank you for your recognition and support of our manuscript.