Cancer treatments, including chemotherapy, in addition to killing a large number of tumour cells, also result in the generation of senescent tumour cells (also called “zombi cells”). While senescent cells do not reproduce, they do, unfortunately, generate a favourable environment for the expansion of tumour cells that may have escaped the effects of the chemotherapy and eventually result in tumour regrowth.
An international team of researchers led by Dr. Manuel Serrano at IRB Barcelona have described how cancer cells that have become senescent after chemotherapy activate the PD-L2 protein to protect themselves from the immune system while recruiting immune suppressor cells. The latter creates an inhibitory environment that impairs the ability of lymphocytes to kill cancer cells. Based on these findings, scientists wondered what would be the effect of inactivating PD-L2. Interestingly, senescent cells lacking PD-L2 are rapidly eliminated by the immune system. This intercepts the capacity of senescent cells to create an immunosuppressive environment and, as a result, lymphocytes retain their full capacity to kill those cancer cells that may have escaped the effects of chemotherapy.
“By blocking PD-L2 in mouse models, we have seen that chemotherapy is more effective against cancer. This finding paves the way to consider the use of a potential PD-L2 inhibitor as an adjuvant in the treatment of this disease,” explains Dr. Manuel Serrano, currently at Altos Labs (Cambridge, United Kingdom).