In a recent study published in the journal PLoS One, a team of researchers from Weill Cornell Medical College have found that lung cancer attracts circulating immune cells to the tumor mass, reprogramming these cells to support its growth and progression.
In their study titled “Identification of Reprogrammed Myeloid Cell Transcriptomes in NSCLC”, Anna Durrans, Dingcheng Gao and colleagues, found a high concentration of myeloid cells (bone marrow-derived immune cells) in lung tumors that were resected from patients with lung cancer. The results from the analysis showed that nested myeloid cells had different genetic features compared to the healthy tissue of about 5 to 10 centimeters adjacent to the tumour. According to the researchers this indicated that myeloid cells had changed their genetic configuration for the cancer to grow.
“Traditional cancer therapies often don’t work well because the cancer continually mutates its genes as a way to escape the drugs,” said in a recent news release co-senior author Dr. Vivek Mittal, associate professor of cell and developmental biology in cardiothoracic surgery at Weill Cornell. “By contrast, immune cells have no mutations. They simply change expression of their genes – which can be turned on or off by drugs, as needed.
“What we found is quite exciting,” added Mittal, who is also director of the Neuberger Berman Foundation Lung Cancer Center Laboratory at Weill Cornell. “We discovered a process within the tumor that suggests we can combine new drugs, such as immunotherapies, with standard treatment.”
“This study highlights how cancer cells can capture and subvert the cells of the immune system in a manner that supports cancer growth,” said co-senior author Dr. Nasser Altorki, director of the Division of Thoracic Surgery at Weill Cornell Medical College and NewYork-Presbyterian/Weill Cornell Medical Center and the Gerald J. Ford-Wayne Isom Research Professor in Cardiothoracic Surgery at Weill Cornell. “An understanding of how that happens will allow us to design treatments that either prevent or reverse these events, thus restoring the capacity of the immune cells to contain and kill the cancer.”
Findings from this study expand on previous work from the research team, which has recently published in the journal Cell Reports data on how lung tumours communicate with their adjacent microenvironment (composed by immune cells, connective tissue, blood vessels and structural cells). This study was the first to determine how tumours reprogram their host immune cells, and this discovery sheds light on potential therapeutic ways of dismantling these networks.
The Weill Cornell and Wistar Institute in Philadelphia researchers aimed to comprehend what occurs to myeloid cells once they live within human lung tumors’ microenvironment. Individual myeloid cells were used and genetic expression was examined to evaluate each gene’s activity. The results revealed that between 80 to 100 genes had a different genetic expression in the myeloid cells found within the lung tumour in comparison to healthy lung tissue.
“This would not have been possible if we had examined whole tumor tissues, and not individual myeloid cells of the tumor,” Mittal said.
“This is a fresh approach because targeting activated genes in these cells may substantially delay or stop tumor growth,” he added, “and would not affect normal cells because these gene targets are not present.” Moreover, targeting these genes may complement existing conventional therapies that specifically target cancer cells.
