Breaking down cancer's defense for future vaccines
The VEGF-C-expresses (lymphangiogenic) tumors. Credit: EPFL
Researchers at the EPFL have identified an important mechanism that could lead to the design of more effective cancer vaccines. Their discovery of a new-found role of the lymphatic system in tumour growth shows how tumours evade detection by using a patient's own immune system.
Tumour cells present antigens or protein markers on their surfaces which make them identifiable to the host immune system. In the last decade, cancer vaccines have been designed that work by exposing the patient's immune cells to tumour-associated antigens and so priming them to kill cells that present those antigens. These have caused much excitement, not least because by acting so specifically on cancer cells, they could potentially eliminate the unpleasant side effects of chemo- and radiotherapy.
Like soldiers protecting a fort
However, clinical trials of such vaccines have had a very low success rate to date, mainly because tumours have various mechanisms for evading detection by immune cells, even when those immune cells called T cells have been primed to seek them out. Those mechanisms are, in general, poorly understood. But in a paper to be published this week in Cell Reports, the laboratories of Melody Swartz at EPFL and Stéphanie Hugues at UNIGE provide a key insight into one of them. They describe for the first time how, like soldiers protecting a fort, lymph vessels surrounding a tumour ward off T cell attack.
Plenty of research has shown that tumours can induce the growth of lymph vessels in their vicinity, and that this growth is correlated with metastasis and poor prognosis. It was assumed that these lymph vessels simply provided an escape route for cancer cells, transporting them to distant sites. In the new study, led by postdoc Amanda Lund, the researchers show that lymph vessels actually suppress the immune response, deleting the attacking T cells or leaving them "functionally exhausted" by the time they reach the tumour.
They studied a type of tumour that expresses large amounts of VEGF-C, a molecule that is naturally expressed in humans and that stimulates lymphatic growth. Having engineered the tumour cells to express a foreign antigen, they compared the efficacy of a vaccine designed to prime T cells to kill cells carrying that antigen, either when VEGF-C was present or when its activity was blocked . With VEGF-C suppressed, the vaccine's efficacy increased and tumour growth slowed fourfold.
A weakness in cancer's defense system exploited
The researchers went on to show that the endothelial cells which line lymph vessels "scavenge" tumour-specific antigens and present them to the tumour-specific T cells in a suppressive manner. This, in turn, promotes the local deletion of those T cells. According to Prof Swartz, that means that first targeting the lymph vessels associated with a tumour could, in theory, significantly increase the efficacy of existing cancer vaccines. "It would be like removing the soldiers from around the fort before sending in your opposing army," she says. "If you disable the lymph vessels' suppressive functions, our data suggest that tumour-killing T cells would do their job a lot more effectively." Future clinical trials are needed to put that theory to the test.
More information: VEGF-C Promotes Immune Tolerance in B16 Melanomas and Cross-Presentation of Tumor Antigen by Lymph Node Lymphatics, Cell Reports.
Provided by Ecole Polytechnique Federale de Lausanne
- New strategy to attack tumor-feeding blood vessels Jun 06, 2011 | not rated yet | 0
- Evidence strengthens link between NSAIDs and reduced cancer metastasis Feb 13, 2012 | not rated yet | 0
- New role for Vascular Endothelial Growth Factor in regulating skin cancer stem cells Oct 19, 2011 | not rated yet | 0
- Light, chemistry, action -- a new technique to target skin cancers? Apr 11, 2011 | not rated yet | 0
- Researchers use human vaccine to cure prostate cancer in mice Jun 19, 2011 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
Ratio of Hydrogen of Oxygen in Dessicated Animal Protein
May 13, 2013 As an experiment, for the past few months I've been consuming at least one portion of Jell-O or unflavored Knox gelatin per day. I'm 64, in very...
Alcohol and acetaminophen
May 13, 2013 Edit: sorry for the typo in the title , can't edit I looked around on google quite a bit and it's very hard to find precise information on the...
Marie Curie's leukemia
May 13, 2013 Does anyone know what might be the cause of Marie Curie's cancer
- More from Physics Forums - Medical Sciences
More news stories
Older prostate cancer patients with other underlying health conditions should think twice before committing to surgery or radiation therapy for their cancer, according to a multicenter study led by researchers in the UCLA ...
Cancer 21 minutes ago | not rated yet | 0 |
Intensity-modulated radiation therapy has become the most commonly used type of radiation in prostate cancer, but research from the University of North Carolina suggests that the therapy may not be more effective than older, ...
Cancer 2 hours ago | not rated yet | 0
New research suggests that a compound abundant in the Mediterranean diet takes away cancer cells' "superpower" to escape death. By altering a very specific step in gene regulation, this compound essentially re-educates cancer ...
Cancer 2 hours ago | 5 / 5 (4) | 0 |
(HealthDay)—For young adults needing either a chest or abdominopelvic computed tomography (CT), the short-term risk of death from underlying morbidity is greater than the long-term risk of radiation-induced ...
Cancer 3 hours ago | not rated yet | 0
In a new study described in the journal Oncogene, researchers reveal how a key player in cell growth, immunity and the inflammatory response can be transformed into a primary contributor to tumor growth.
Cancer 8 hours ago | not rated yet | 0 |
University of Minnesota Medical School researchers from the Masonic Cancer Center, University of Minnesota, in partnership with the University's Brain Tumor Program, have developed a new mouse model of malignant peripheral ...
24 minutes ago | not rated yet | 0 |
Turns out, that old "practice makes perfect" adage may be overblown. New research led by Michigan State University's Zach Hambrick finds that a copious amount of practice is not enough to explain why people ...
34 minutes ago | 5 / 5 (2) | 0 |
A new diagnostic test for a worm infection that can lead to severe enlargement and deformities of the legs and genitals is far more sensitive than the currently used test, according to results of a field ...
21 minutes ago | not rated yet | 0 |
Study shows that women who smoke during pregnancy increase the risk of both obesity and gestational diabetes in their da
Women who smoke during pregnancy increase the risk of both obesity and gestational diabetes, in their daughters, concludes research published in Diabetologia, the journal of the European Association for the Study of Diabet ...
5 minutes ago | not rated yet | 0
While Huntington's disease (HD) is currently incurable, the HD research community anticipates that new disease-modifying therapies in development may slow or minimize disease progression. The success of HD research depends ...
23 minutes ago | not rated yet | 0
Vermont became on Monday the third US state to legalize physician-assisted suicide.
17 minutes ago | not rated yet | 0