Aug. 11 (UPI) — A combination of two cancer treatments to target immune cells involved with the formation of lung tumors could provide an effective treatment for lung cancer, according to a study published Wednesday in Science Translational Medicine.
The chemotherapy drug cisplatin, in combination with a new immune therapy called CSF1R antibody, may provide an effective treatment for lung cancer, researchers said.
Their discovery could provide a way for some immunotherapies — which are designed to boost the body’s defenses against cancer — to be more effective in treating lung cancer, they said.
Specifically, if confirmed in future studies, their findings could boost the effectiveness of immune checkpoint blockades, which are a class of drugs commonly used in lung cancer, according to the researchers.
“Unfortunately, only about a fifth of patients with lung cancer benefit from immune checkpoint blockade, and long-lasting responses are rare,” study co-author Amaia Martinez-Usatorre said in a press release.
However, with this combination, “we were actually able to induce the regression of about 70% of the tumors,” said Martinez-Usatorre, post-doctoral fellow at the Swiss Federal Institute of Technology in Lausanne.
Lung cancer is the leading cause of cancer-related death in the United States, according to the American Cancer Society.
Most treatments involve immunotherapy, often in combination with chemotherapy, but they rarely slow progression of the disease, Martinez-Usatorre and her colleagues said.
Immune checkpoint blockade drugs, which are approved to treat lung cancer, are designed to push immune cells called CD8 T to attack the tumor, the researchers said.
However, if there are not enough CD8 T cells in the tumor, which is often the case in lung cancer, the treatment will not be effective, they said.
Using animal models with lung cancer genetically engineered to have mutations found in human disease, the researchers experimented with using anti-angiogenic drugs to boost CD8 T cell levels.
Angiogenesis is the process by which blood vessels form and grow in tumors, causing the tumors to grow, according to the researchers.
In a study published in 2017 by Science Translational Medicine, the same team of researchers determined that the approach, which is designed to induce angiogenesis, worked in breast cancer, and it has also been shown to be effective in liver cancer, they said.
However, the researchers found that this drug combination did not work in the lung cancer — instead, it appeared to make the tumors “grow faster” by activating another type of immune cells called Treg, which effectively “thwart” CD8 T cells, Martinez-Usatorre said.
To counter this, the researchers sought to identify potential vulnerabilities in Tregs, and found that their survival in tumors depended on another type of immune cell, called macrophages.
“When we analyzed human lung cancer datasets, we found that the more macrophages, the more Tregs there were in the lung tumors,” Martinez-Usatorre said.
“Macrophages and Tregs establish a dangerous liaison in lung cancer [and] to enhance the efficacy of immune checkpoint blockade, we’d need to break up this liaison,” she said.
One type of tumor-associated macrophage expressed the protein CSF1R and needed it to survive, their experiments showed.
They were able to eliminate this macrophage from lung tumors by using an antibody designed to block CSF1R, the researchers said.
A second type of macrophage found in lung tumors did not rely on CSF1R and thus was not affected by the antibody. However, it was sensitive to the chemotherapy cisplatin, which commonly is given to patients with lung cancer.
When used in combination, cisplatin and the CSF1R antibody eliminated both macrophage types and left very few macrophages in the tumors, the researchers said.
As a result, the tumor Tregs were also eliminated, allowing CD8 T cells to remain in the tumors, slowing their growth, they said.
“This combination is promising and could be tested in patients with lung cancer,” study co-author Michele De Palma.
“Because the drugs we used in this experiment — cisplatin and the CSF1R antibody — are approved treatments for certain human diseases, this could expedite clinical testing of the strategy,” said De Palma, a biologist at Swiss Federal Institute of Technology.