Pancreatic cancer cells release signal to suppress immune system's attack on tumors

Pancreatic cancer cells release signal to suppress immune system's attack on tumors

A key immune signal has a previously unknown role in turning off the immune system's attack on pancreatic cancer cells, a new study finds. Led by researchers at NYU Grossman School of Medicine, the study found that an immune signaling protein, interleukin-1β (IL-1β), is made and released by pancreatic tumor cells. This was shown to reduce anti-cancer immune responses, which promoted the growth of pancreatic ductal adenocarcinoma or PDA, a form of cancer that is usually deadly within two years. Published online in Cancer Research , a journal of the American Association for Cancer Research, on January 8, the study found that blocking the action of IL-1β in mice with immune proteins called antibodies caused a 32 percent decrease in PDA tumor growth. Other experiments combined the anti-IL-1β antibody, which gloms onto and neutralizes its target, with an already approved antibody treatment that shuts down the protein "checkpoint" called PD1. To spare normal cells from immune attack, the immune system uses "checkpoints" on immune cells that turn them off when they receive the right signal. Cancer cells hijack checkpoints to turn off the system, leading to immune suppression of CD8+ T cells that would otherwise kill cancer cells. Therapies called checkpoint inhibitors counter this effect. While effective against many cancers, checkpoint inhibitors have failed in PDA, with the response rate in tumors as low as roughly three percent in some trials, and the limitations attributed to poor CD8+ T cell infiltration and immune suppression. In the current study, adding anti-IL-1β antibodies to anti-PD-1 antibody treatment doubled the infiltration of such T cells into PDA tumors and increased the anti-tumor activity of PD-1 blockade by 40 percent. By engineering mice with versions of PDA that lack the IL-1β gene, we found for the first time that pancreatic cancer cells produce IL-1β, and that it is essential for the continued growth of PDA tumors. Blocking IL-1β with an antibody treatment may represent another way to make pancreatic tumors vulnerable to the immune system, with the potential to significantly increase the effectiveness of checkpoint inhibitors if combined." Dafna Bar-Sagi, PhD, study senior author, Vice Dean for Science and Chief Science Officer for NYU Langone Health Initial trigger



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