Promoting anti-tumor immunity via the immunostimulatory cytokine LIGHT may highly benefit colon cancer patients whose tumor — having spread to the liver — now face palliative care as their only option.
In mice, increasing LIGHT expression in colon tumors or liver metastasis helped activate tumor-killing T-cells, triggering the regression of established tumors and slowing the growth of liver metastasis.
The study by researchers at the University of Illinois at Chicago (UIC), “LIGHT elevation enhances immune eradication of colon cancer metastases,” appeared in Cancer Research.
Colon cancer is the second leading cause of cancer-related deaths in the United States, in part because by the time most patients are diagnosed, the cancer as already spread to other areas of the body and is more difficult to eradicate. The most common site of metastasis in colon cancer patients is the liver.
“For most patients with colon cancer that has spread to the liver, current treatments are palliative and not curative,” Ajay Maker, MD, associate professor of surgery in the UIC College of Medicine and the study’s corresponding author, said in a press release. “And while studies have suggested that immunotherapy may be a promising approach for advanced cancers, the use of such treatments for advanced gastrointestinal metastases have not yet been very successful.”
Studies have shown that expression of the immunostimulatory protein LIGHT in the microenvironment of colon cancer liver metastasis is significantly associated with overall survival and recurrence-free survival.
This led Maker and his team to hypothesize that increased LIGHT expression in the tumor microenvironment could lead to T-cell infiltration into colorectal tumors and liver metastasis, which could result in immune-mediated tumor regression.
Maker and colleagues established colon cancer and liver metastasis in mice and found that indeed it was the case. Mice in which the expression of LIGHT was turned on in the tumor microenvironment had a rapid infiltration of T-cells, resulting in a sustained reduction of tumor size.
“We demonstrated that delivery of a therapeutic immune-stimulating cytokine caused T-cells to traffic to tumors and to become activated tumor-killing cells,” Maker said. “This activity is especially exciting because it resulted in a profound anti-tumor immune response without any other chemotherapy or intervention. The treatment manipulates our natural defenses to fight off the tumor in the same way it has been trained to attack other foreign invaders in our body.”
The findings have great clinical potential for a patients with very poor prognosis. Further studies looking at ways to increase the expression of LIGHT in the tumor microenvironment are now warranted.