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

April 3, 2017, Baylor College of Medicine
Blood vessel with an erythrocyte (red blood cell, E) within its lumen, endothelial cells forming its tunica intima (inner layer), and pericytes forming its tunica adventitia (outer layer) Credit: Robert M. Hunt/Wikipedia/CC BY 3.0

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 have discovered that tumor blood vessels and the immune system influence each other's functions, and propose that considering these bilateral effects in cancer therapy might improve outcomes. The study appears in Nature.

"One of the characteristics of successful cancerous tumors is their ability to trigger the formation of new , a process called angiogenesis, to supply oxygen and nutrients to the growing cell mass," said corresponding author Dr. Xiang Zhang, associate professor of molecular and cellular biology and the Lester and Sue Smith Breast Center at Baylor. "Therapies that aim at blocking angiogenesis to starve the can retard its growth; however, they can also have an undesired effect, and resistance to treatments."

To better understand this apparent contradiction, Zhang and colleagues have taken a closer look at the tumor microenvironment in breast cancer.

Blood vessels and the immune system talk to each other

"We are trying to uncover a more complete picture of the tumor microenvironment in breast cancer," said Zhang, who is also a McNair Scholar at Baylor. "The tumor environment includes and other types of cells that are recruited to the tumor mass and help the tumor grow. Scientists have divided those cells into subpopulations and studied them separately. We think that for a more complete understanding of the entire tumor microenvironment we have to study it with all its cell types together. Here, we applied this approach and discovered for the first time connections between tumor blood vessels and the immune system."

Despite their abundance, tumor blood vessels perform their job poorly because their structure and functions are abnormal. For instance, they do not carry enough blood to the tumor which limits the amount of oxygen and nutrients and creates a harsh microenvironment that can stimulate some cancer cells to escape through gaps in blood vessels and lead to metastasis. Abnormal tumor blood vessels may also interfere with anti-tumor or drugs attempting to reach the tumor.

Recently, restoring ' function and structure to normal, a process called normalization, has been considered a promising strategy to improve anti-blood vessel therapies. Vessel normalization can potentially limit or prevent cancer progression and metastasis, and improve the response to immunotherapy, chemotherapy and radiation therapy. However, little is known about how the tumor microenvironment regulates vessel normalization.

By applying their approach of studying the tumor microenvironment as a whole, Zhang and his colleagues discovered that immune cells called T lymphocytes can promote the process of vessel normalization.

"The reciprocal regulation is also true," Zhang said. "If we change the structure of the vasculature of the tumor toward vessel normalization, then we can also stimulate T cells to infiltrate the tumor. This bidirectional regulation between blood vessels and the immune system had not been elucidated before."

Implications for cancer therapy

"Both anti-blood vessel therapies and immunotherapies have been used in the clinic and have different degrees of success," said Zhang. "For instance, immunotherapy has been successful in some types of cancer such as melanoma and lung cancer, which are very aggressive cancers that did not have effective treatment until these therapies came along. However, there are still many patients who do not respond to this type of therapy. Similarly, from the anti-blood vessel we know that many attempts have not been as successful as anticipated, and we have not been able to understand why."

The researchers work suggests that therapies should consider not only, for instance, the presence of immune cells and their activities in the , but also the vascular structure of the tumor because it has implications of whether the tumor would be able to respond to immunotherapy.

"Our finding suggests that anti- therapies toward the vessels most likely influence the anti-tumor immune response, and vice-versa. Therefore, there is a possibility that by combining the therapies we can achieve better outcomes," Zhang said. "However, we are still far from having practical clinical solutions. We hope that our work will provide some therapeutic theoretical basis for those researchers using the two different therapies to collaborate and look at each other's biomarkers and therapeutic strategies."

Explore further: Restoring flawed tumor vessels could lead to better cancer treatments

More information: Lin Tian et al, Mutual regulation of tumour vessel normalization and immunostimulatory reprogramming, Nature (2017). DOI: 10.1038/nature21724

Related Stories

Restoring flawed tumor vessels could lead to better cancer treatments

November 17, 2016
Researchers led by Peter Carmeliet (VIB-KU Leuven) have found a novel way to normalize the dysfunctional blood vessels that are typical for tumors. Those vessels play a pivotal role in cancer metastasis, as their fragility ...

Growing tumors put the pressure on nutrient-supplying blood vessels

January 26, 2017
Mechanical pressure caused by cancer growth plays a key role in the development and distribution of blood vessels in tumors, according to a new UCL (University College London) study published in PLOS Computational Biology.

Tumor blood vessel protein provides potential therapeutic target

August 27, 2014
Tumor blood vessels supply oxygen and nutrients to cancer cells and provide access to other organs. While tumor vasculature shares many features with normal vessels, their unique characteristics are potential therapeutic ...

Cancer cells' transition can drive tumor growth, researchers find

December 21, 2016
As cancerous tumors fester in the body, they need an ever-increasing blood supply to deliver the oxygen and nutrients that fuel their growth. Now, a team led by University of Florida Health researchers has established how ...

Silencing cancer cell communication may reduce the growth of tumors

January 30, 2017
In several types of cancer, elevated expression of the chemokine receptor CCR4 in tumors is associated with poor patient outcomes. Communication through CCR4 may be one mechanism that cancer cells use to create a pro-tumor ...

The antibody that normalizes tumor vessels

December 12, 2016
An important parcel must be delivered to the correct place. It is so important that it can be a question of life or death. However, uneven streets and missing railings risk to bring it off the road and leave it undelivered. ...

Recommended for you

Scientists grow functioning human neural networks in 3-D from stem cells

October 18, 2018
A team of Tufts University-led researchers has developed three-dimensional (3-D) human tissue culture models for the central nervous system that mimic structural and functional features of the brain and demonstrate neural ...

Functional engineered oesophagus could pave way for clinical trials 

October 18, 2018
The world's first functional oesophagus engineered from stem cells has been grown and successfully transplanted into mice, as part of a pioneering new study led by UCL.

New findings cast light on lymphatic system, key player in human health

October 16, 2018
Scientists at the Oklahoma Medical Research Foundation have broken new ground in understanding how the lymphatic system works, potentially opening the door for future therapies.

New model suggests cuffless, non-invasive blood pressure monitoring possible using pulse waves

October 16, 2018
A large team of researchers from several institutions in China and the U.S. has developed a model that suggests it should be possible to create a cuffless, non-invasive blood pressure monitor based on measuring pulse waves. ...

Age-related increase in estrogen may cause common men's hernia

October 16, 2018
An age-related increase in estrogen may be the culprit behind inguinal hernias, a condition common among elderly men that often requires corrective surgery, according to a Northwestern Medicine study was published Oct. 15 ...

Income and wealth affect the mental health of Australians, study shows

October 16, 2018
Australians who have higher incomes and greater wealth are more likely to experience better mental health throughout their lives, new research led by the Bankwest Curtin Economics Centre has found.

0 comments

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.