Ludwig Cancer research study finds way to revive potent immune cells for cancer therapy

MAY 24, 2021, NEW YORK - A Ludwig Cancer Research study has discovered how to revive a powerful but functionally inert subset of anti-cancer immune cells that are often found within tumors for cancer therapy. Led by Ludwig Lausanne's Ping-Chih Ho and Li Tang of the École Polytechnique Fédérale de Lausanne, the study describes how an immune factor known as interleukin-10 orchestrates the functional revival of "terminally exhausted" tumor-infiltrating T lymphocytes (TILs), which have so far proved impervious to stimulation by immunotherapies. It also demonstrates that the factor, when applied in combination with cell therapies, can eliminate tumors in mouse models of melanoma and colon cancer. The findings are reported in the current issue of Nature Immunology. "We've found, for the first time, that terminally exhausted TILs can be directly rejuvenated so that their potent anti-cancer activity is restored, and that this rejuvenation is accomplished through the metabolic reprogramming of the cells induced by interleukin-10," said Ho, associate member of the Ludwig Institute for Cancer Research, Lausanne. Deprived of oxygen and vital nutrients within tumors, the TILs most capable of killing cancer cells are typically pushed into a stubbornly sluggish state known as exhaustion. Recent research has identified two distinct types of exhausted TILs. One, known as "progenitor exhausted" TILs, can recognize cancer cells with nominal efficiency and proliferate in response to the immunotherapy PD-1 blockade. But it is their descendants, "terminally exhausted" TILs, that are best equipped to detect and destroy cancer cells. They are, however, functionally disabled, prone to self-destruction and utterly incapable of proliferation. "Even PD-1 blockade cannot restore the function of these terminally exhausted TILs," said Ho. "In fact, many patients do not respond to PD-1 blockade because their tumors lack progenitor exhausted TILs and have only terminally exhausted TILs. This is why researchers are looking for ways to revive terminally exhausted T cells for cancer therapy." Three lines of evidence prompted the current study. First, Ho and his team recently END