CDI Scientist and Colleagues Demonstrate Better Immune Memory Cell Workings

A scientist at the Hackensack Meridian Center for Discovery and Innovation (CDI) who specializes in immunology has published new findings with colleagues about a little-understood mechanism of the immune system which could pave a way to better cancer treatments and vaccines of the future.

The new findings by Hai-Hui “Howard” Xue, Ph.D., a faculty member of the CDI, show that “memory” CD8+ T cells acquire new binding sites of a specific protein which enables them to provide long-lasting immune responses to germs and cellular threats once the body has encountered them, according to the latest paper, in the Proceedings of the National Academy of Sciences, which complements a February study on the same mechanism in the Journal of Experimental Medicine.

The protein in question: the CCCTC-binding factor, known as CTCF, which bolsters the “memory,” in the memory T cells, according to the findings. CTCF gains new binding sites in CD8+ T cells after activation by pathogens and remains at these new locations in memory  CD8+ T cells. An immediate impact of the CTCF at these new binding sites is to mediate important interactions of chromatin which in turn help genetic programming to boost immune regulations.

Taken together, the cells become boosted for the threat when it is seen again. This has clear implications for vaccines; but there could also be applications for fighting cancer.

“Our findings suggest that these CTCF-mediated actions prepare memory CD8+ T cells for heightened responsiveness to antigen restimulation, which may be explored as a therapeutic target to achieve enhanced anti-viral and anti-tumor immunity,” the scientific team writes.

The new PNAS paper also follows a pair of studies Xue and his lab published in Nature Immunology in 2022, which focused on a complementary mechanism in T cells. The first paper pointed toward a way to improve the “memory” of these cells – meaning potentially improving vaccines and boosting immune responses in future encounters with the same pathogens; the second paper delved further into the complex mechanisms underlying these interactions.