Mixed signals impair communications of all sorts—including communications between immune cells struggling to fend off cancer. According to a new study led by scientists at the University of California, Irvine, mixed signals between cytotoxic T cells and immunosuppressive T cells—specifically, CD8 cells and T regulatory (Treg) cells—can weaken the response to checkpoint immunotherapy. Indeed, the scientists have found that interrupting CD8 -to-Treg signaling before PD-1 immunotherapy “improves control over immunogenic melanoma.
” These findings appeared June 10 in , in an article titled, “ .” “[We] show that PD-1 blockade increases tumor-Tregs in mouse models of melanoma and metastatic melanoma patients,” the article’s authors wrote. “Mechanistically, Treg accumulation is not caused by Treg-intrinsic inhibition of PD-1 signaling but depends on an indirect effect of activated CD8 T cells.
” “CD8 T cells produce IL-2 and colocalize with Tregs in mouse and human melanomas,” the authors explained. “IL-2 upregulates the anti-apoptotic protein ICOS [inducible co-stimulator] on tumor-Tregs, promoting their accumulation.” According to the scientists, their findings suggest a new strategy that could enhance the therapeutic effectiveness of checkpoint therapy, such as PD-1 blockade, which has become the standard of care for metastatic melanoma.
While this treatment is effective in 40% of patients, the other 60% develop resistance, leading to tumor regrowth..