On August 12, Liu Wenxian's research group published a research paper
entitled Myc inhibition tips the immune balance to promote antitumor immunity in the immunology journal Cellular & Molecular Immunology.

Myc as the most famous proto-oncogene has always been the focus of research, but in the past in the Myc as the core of the anti-tumor research most of the work is to take the tumor cells themselves as the main body of research, ignoring the function of
Myc in the immune system, especially in the tumor microenvironment in the anti-tumor response.

After treating the tumor-bearing mice with Myc's inhibitor Mycro3, the researchers in Professor Liu Wenxian's research group found that the regulatory T cells (Tregs) in the tumor microenvironment were significantly reduced, CD8+ T cells were significantly increased, and the tumor growth was slow
。 To further reveal the mechanism of Mycro3's anti-tumor response, the researchers used single-cell sequencing techniques combined with mouse genetics as well as in vivo & in vitro functional experiments to demonstrate that Myc is indispensable for regulatory T cells (Treg) to perform their inhibitory function, and that the anti-tumor effect of Mycro3 is achieved
by inhibiting Treg in the tumor microenvironment 。 Not only that, further experimental results show that different T cell subsets have different sensitivities to Myc's inhibitor Mycro3 in the tumor microenvironment, and the strength of the sensitivity is determined by the amount of
Myc protein expression 。 Regulatory T cells have lower expression of Myc protein than CD8+ T cells, so under the same Mycro3 treatment conditions, relatively few Myc proteins in Treg cells are easily fully bound by Mycro3 and thus inhibit Myc protein binding to Max protein to form a functional complex, while CD8+ T cells are less
inhibited due to having a relatively large number of Myc proteins 。 This phenomenon gives Myc inhibitors the targeting of specific inhibition of regulatory T cells, thereby breaking the balance between regulatory T cells and CD8+ T cells in the tumor microenvironment, lifting the inhibition of regulatory T cells on CD8+ T cells and thus enhancing the killing ability
of CD8+ T cells to tumors.

The study takes the function of the proto-oncogene Myc in the anti-tumor immune response as the core of the study, and for the first time proves that the sensitivity of different T cell subsets to Myc inhibitors in the tumor microenvironment is determined by the expression of Myc protein
, and the difference between Trg and CD8+ T for Myc inhibitor sensitivity in the tumor microenvironment is used to break the immune balance and enhance the anti-tumor immune response.

PhD students Chao Yang and Yun Liu, and Yudi Hu, a master's student in medical school, are co-first authors
of the paper.
Professor Wenxian Liu, Professor Qiyuan Li of the School of Medicine, Dr.
Changchun Xiao, Head of Sanofi China Research Institute, and first author Chao Yang are co-corresponding authors
of this article.
The research has been strongly supported by the Biomedical Instrument Sharing Platform and the Center for Laboratory Animals of Xiamen University, and has been funded
by the National Natural Science Foundation of China, the National High-level Talents Youth Program and the Basic Scientific Research Business Expenses of Central Universities.

Full text link to the original article: https://doi.
org/10.
1038/s41423-022-00898-7