A team of researchers from the Perelman School of Medicine and several other institutions recently reported a significant reduction in tumor growth in myeloid immune cells using an experimental treatment on mice.
The article that appeared in Nature Cancer described how inhibiting the c-Rel molecule that promotes immune responses within myeloid cells blocks immune suppressor cell production.
Currently, immunotherapies target lymphoid cells. The new discovery relied on checkpoint inhibitors, a type of immunotherapy, to target myeloid cells in a mouse model and human cells.
Dr. Youhai Chen, a professor at Perelman and senior author of the study, described their c-Rel discovery. The team had been studying c-Rel’s relationship to autoimmune diseases and inflammation for almost two decades.
Just a short while ago they began to see c-Rel’s association with myeloid-derived suppressor cells (MDSCs).
MDSCs are normally an important barrier to infections. However, when cancer strikes these myeloid cells reverse and function together with tumor cells. This combination is largely responsible for tumor progression and reducing the ability of the immune system to fight cancer.
Results of the Study
Dr. Chen’s previous work with c-Rel provided a convenient transition to analyzing whether c-Rel had an active role in the growth of cancer. Dr. Chen announced that the results of their new analyses were “unexpected and surprising.”
It was unexpected because c-Rel has always been known to promote immune responses. It had not been known to suppress the immune system.
This finding led Dr. Chen and his team to discover a new drug inhibitor that is effective in targeting certain cancers.
The results were truly astounding. Mice who were deficient in c-Rel had a reduction in tumor size and weight of about eighty percent.
Treating a second set of mice with the drug that inhibits c-Rel saw tumors shrink about seventy percent. Both studies used controls as a comparison against the drug.
When Cancer Attacks the Body
Dr. Chen’s group gave evidence of the new drug’s potential as well as discovering how tumor cells decreased c-Rel. In doing so, MDSCs are produced, preventing the immune system from attacking the cancer.
The newly developed drug puts the immune system back into action.
A Different Approach
The REL gene has been known to block tumor growth and was found to reduce MDSC in mice.
When the researchers deleted the REL gene in mice, it proved this theory.
A One-Two Punch
When the team again tested the new inhibitor drug, they found that the drug showed marked improvement when it was combined with a checkpoint inhibitor drug called anti-PD-L1.
A checkpoint inhibitor drug reverses the hold that cancer cells put on the immune system. This combination proved to be most effective in suppressing tumor growth.
Anti-PD-L1 treatments have only a temporary effect on tumors. But Dr. Chen explains that the combination of Anti-PD-L1 combined with the new c-Rel drug has the potential to extend lives.
And Now the Next Step
The team has proven the efficacy of the inhibitor drug in animal models. Now it is imperative to give an assessment of the drug’s safety prior to beginning human clinical trials.
Dr. Chen suggests that this new class of checkpoints involving a distinctly different immune system cell may have a definite impact on the field of immunotherapy.