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On February 14, 2022, the team of Professor Wang Chenhui from the School of Life Science and Technology of Huazhong University of Science and Technology published the title "Cancer cell-expressed BTNL2 facilitates tumor immune escape via engagement with IL-17Aproducing γδ T cells" in the international authoritative journal "Nature Communications" latest research results
.
In recent years, tumor immunotherapy has made rapid progress
.
Among them, immune checkpoint inhibitors at the forefront of tumor immunotherapy (mainly including two types of immune checkpoint inhibitors, CTLA-4 and PD-1/PD-L1) have shown good efficacy in a variety of cancer types
Butyrophilin-like 2 (BTNL2) is a type I transmembrane immunomodulatory protein that is highly expressed in the gut and belongs to the butyrophilin-like family
.
Previous studies reported that the BTNL2-Fc fusion protein was able to directly inhibit the activation of CD4+ T cells
Through research, we found that BTNL2 promotes the production of IL-17A by acting on the γδ T cell population in the tumor microenvironment, and IL-17A leads to the reduction of cytotoxic CD8+ T cell infiltration by recruiting MDSCs, thereby inhibiting anti-tumor immunity
.
After blocking BTNL2 with a novel monoclonal neutralizing antibody, we found that it has a significant therapeutic effect on a variety of mouse tumors, and has a certain synergistic therapeutic effect with anti-PD-1 antibody inhibitors
There are still some important scientific questions in this work to be further studied in the future: 1) What molecule is the receptor of BTNL2 on the surface of T cells? 2) Our study and many previous studies have found that BTNL2 can directly inhibit the activation of CD4+ T cells and CD8+ T cells.
What is the mechanism of its inhibition of T cell activation? Does this mechanism also play a role in antitumor immune escape? 3) This study mainly adopts the mouse subcutaneous tumor model
.
Does BTNL2 also play a role in spontaneous tumor or drug-induced tumor models? Is the mechanism of action different from that of subcutaneous tumors? 4) The single nucleotide polymorphisms or expression changes of BTNL2 are associated with the susceptibility of prostate cancer, melanoma, breast cancer and other cancers.
Doctoral student Du Yanyun and Ph.
D.
student Peng Qianwen from the School of Life Sciences of Huazhong University of Science and Technology are the co-first authors of the paper
.
Huazhong University of Science and Technology is the first unit of the thesis
Paper link: https://doi.
