Possible new immune therapy target in lung cancer

October 18, 2017, University of Bern
Fluorescence microscopy images of blood vessels supported by perivascular cells. The top row shows vessels with perivascular cells from normal lung tissue compared to vessels supported by tumor-derived perivascular cells (bottom row). The vessels on the bottom show a higher leakage. Credit: Bern University Hospital/University of Bern

A study from Bern University Hospital in collaboration with the University of Bern shows that so-called perivascular-like cells from lung tumors behave abnormally. They not only inadequately support vascular structures, but also may actively modulate the inflammatory and immune response. These findings may represent a novel stromal cancer target.

Lung cancer accounts for the highest number of cancer-related deaths, with an estimated 1.6 million deaths in 2012 worldwide. Among different types of lung cancer, non-small cell lung cancer (NSCLC) is the most prevalent. Recent advances in genetic analyses led to targeted treatments that work very effectively in cases where tumors carry a specific targetable mutation. Another promising strategy focuses on redirecting the to recognize and attack . Despite these promising approaches, there is still a need to better understand the dynamics that lead to lung cancer progression.

A research team from the Division of General Thoracic Surgery, Bern University Hospital that is also affiliated with the Department for Biomedical Research, as well as the ARTORG Center for Biomedical Research of the University of Bern found that perivascular play an important role in tumor progression. Their findings could lead to a novel immune therapy target in lung cancer. The results of the study have been published in Scientific Reports.

Perivascular cells are supporting the tumor

"There is increasing evidence for a link between perivascular cells and tumor growth, that's why we were trying to find it", says Sean Hall from the Thoracic Surgery Research Lab, Bern University Hospital. NSCLC specimens were collected from patients that underwent surgery at the Division of General Thoracic Surgery, Bern University Hospital. In the laboratory, he then isolated the perivascular cells from the lung tissues.

In comparison with the same cell type isolated from normal tissue, perivascular cells from NSCLC lesions showed several abnormalities. Interleukin-6, a pro-inflammatory cytokine, was upregulated, as was PD-L1, a targetable immune-checkpoint-inhibitor. "These findings suggest that perivascular cells in NSCLC actively modulate the inflammatory and immune response", says first author Colette Bichsel from the ARTORG Center for Biomedical Engineering Research.

Leaking blood vessels

Next, the research team wanted to see how these cells fulfill their function of supporting blood vessels. To test this, Colette Bichsel developed a chip on which blood vessels can be grown and maintained in the lab. Blood vessels were successfully grown using both NSCLC-derived and normal perivascular cells as supporting cells. But there was one important difference: blood vessels with tumor-derived perivascular cells were leakier than normal . "This shows that tumor pericytes inadequately support vascular structures, which may increase the likelihood of tumor cell evasion", explains Bichsel.

Taken together, the findings from this study show for the first time that perivascular cells play an important role in promoting a pro-inflammatory and immune-suppressing microenvironment. Further studies are needed to evaluate if they may present a target for new treatments.

Explore further: New drug to supercharge immune cells in the fight against cancer

More information: Colette A. Bichsel et al. Increased PD-L1 expression and IL-6 secretion characterize human lung tumor-derived perivascular-like cells that promote vascular leakage in a perfusable microvasculature model, Scientific Reports (2017). DOI: 10.1038/s41598-017-09928-1

Related Stories

New drug to supercharge immune cells in the fight against cancer

September 28, 2017
A new cancer treatment with the ability to normalise tumour blood vessels and boost the body's immune system has been developed by researchers from The University of Western Australia and the Harry Perkins Institute of Medical ...

Tumor-associated neutrophils boost anti-tumor immune responses

November 11, 2014
Lung cancer is a leading cause of cancer-related deaths in both men and women, and survival depends on the stage of cancer at diagnosis. An inflammatory response is induced following tumor formation, and the immune cells ...

Hybrid immune cells in early-stage lung cancer spur anti-tumor T cells to action

July 14, 2016
The microenvironment of tumors is a mix of cell types, mostly comprised of inflammatory cells. White blood cells, recruited from the blood and bone marrow, represent a significant portion of these inflammatory cells and influence ...

Blood vessels and the immune system talk to each other; implications for cancer treatment

April 3, 2017
Some cancer therapies aim at stopping tumor growth by affecting the blood vessels that nurture the tumor mass, while others act on the immune system attempting to eliminate the tumor. Researchers at Baylor College of Medicine ...

Cells that make blood vessels can also make tumors and enable their spread

June 19, 2017
While it's widely held that tumors can produce blood vessels to support their growth, scientists now have evidence that cells key to blood vessel formation can also produce tumors and enable their spread.

White blood cell count predicts response to lung cancer immunotherapy

May 4, 2017
White blood cell counts can predict whether or not lung cancer patients will benefit from immunotherapy, according to research presented at the European Lung Cancer Conference (ELCC).

Recommended for you

Researchers stop spread of cancer in mice by blocking specific molecules

November 21, 2018
Melanoma skin cancer tumors grow larger and are more likely to metastasize due to interactions between a pair of molecules, according to experiments in mice and human cells. The results may restore the potential for a type ...

A study suggests that epigenetic treatments could trigger the development of aggressive tumours

November 20, 2018
A study headed by the Institute for Research in Biomedicine (IRB Barcelona) and published in the journal Nature Cell Biology examined whether the opening of chromatin (a complex formed by DNA bound to proteins) is the factor ...

'Druggable' cancer target found in pathway regulating organ size

November 20, 2018
It's known that cancer involves unchecked cell growth and that a biological pathway that regulates organ size, known at the Hippo pathway, is also involved in cancer. It's further known that a major player in this pathway, ...

Redefining colorectal cancer subtypes

November 20, 2018
There is a long-standing belief that colorectal cancer (CRC), which causes some 50,000 deaths in the United States each year, can be categorized into distinct molecular subtypes. In a paper published recently in the journal Genome ...

Proposed cancer treatment may boost lung cancer stem cells, study warns

November 20, 2018
Epigenetic therapies—targeting enzymes that alter what genes are turned on or off in a cell—are of growing interest in the cancer field as a way of making a cancer less aggressive or less malignant. Researchers at Boston ...

New drug discovery could halt spread of brain cancer

November 19, 2018
The tissues in our bodies largely are made of fluid. It moves around cells and is essential to normal body function.


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.