Mechanism for more efficient cancer treatment decoded
(Medical Xpress) -- A research team from the Institute for Cancer Research at the MedUni Vienna has decoded a previously unknown mechanism of the active ingredient imiquimod in tumour defence. They have been able to prove that imiquimod transforms plasmacytoid dendritic cells (pDCs) into tumour-killers which can fight the tumour independently from other immune cells. This discovery could be an important step on the way to a more efficient treatment for cancer.
The scientist, Barbara Drobits, one of the doctorate students of the Inflammation and Immunity doctorate lecture course promoted by the FWF (Austrian Science Fund) and the MedUni Vienna, and her colleagues, have researched, under the leadership of Maria Sibilia, Head of the Institute, which mechanisms are set into operation when skin cancer is treated with imiquimod. In doing so mast cells in the skin are stimulated which produce the signal protein CCL2. This causes immune cells, in particular plasmacytoid dendritic cells (pDCs) to be recruited to the skin being treated. Imiquimod activates these pDCs through a specific receptor of the congenital immune system, the so-called toll-like receptor (TLR) 7, whereupon the pDCs produce and discharge interferon alpha (IFNa). IFNa also affects the pDCs themselves and stimulates them to emit cytolytic molecules which shoot holes into the tumours wall, perforating it and thereby attacking the tumour cells.
With imiquimod we can therefore make the pDCs enter the tumour on the one hand and attack the tumour cells on the other. The medication therefore acts as an activating signal for the congenital immune system, explains Drobits.
Only little had previously been known about the working mechanism of imiquimod and the positive effect of the pDCs in tumour defence. Says Sibilia: We have shown for the first time that the pDCs are good and helpful and attack the tumour cells, without requiring the adaptive immune system (note: B and T cells) for this. The MedUni Vienna researchers have furthermore been able to prove in process of elimination and in vivo that the mechanism does not function even if only one of the factors is missing, meaning, if for example no TLR7 or no interferon alpha is involved.
In this model with imiquimod, however, it is not possible to eliminate the tumour entirely. However, if we administer the active ingredient in addition to conventional cancer treatment, that could increase the efficiency and thereby reduce the duration of treatment. Furthermore our discovery is an impetus for further studies at the MedUni Vienna, says Sibilia. As it is still not known, whether the effect, which we have been able to prove in melanomas, also occurs in other tumours. A study which looks into this question has already been started at the Institute for Cancer Research.
Imiquimod is a medication from the antiviral group, which is used for the treatment of small, superficial basal cell skin cancer, melanomas or actinic keratosis (damage of the epidermis through many years of intensive exposure to UV radiation). Imiquimod is an immunomodulator which activates the skins immune system, so that it fights viruses or tumours. In Europe, the active ingredient is known as a medication under the Aldara trade name.
More information: Imiquimod clears tumors in mice independent of adaptive immunity by converting pDCs into tumor-killing effector cells. Barbara Drobits, Martin Holcmann, Nicole Amberg, Melissa Swiecki, Roland Grundtner, Martina Hammer, Marco Colonna, Maria Sibilia.. J Clin Invest. doi:10.1172/JCI61034
Provided by Medical University of Vienna
- New model will open immune cell's secrets Dec 23, 2010 | not rated yet | 0
- A new mechanism regulates type I interferon production in white blood cells Jan 12, 2009 | not rated yet | 0
- Cells use allergic response to protect against cancer-causing damage Dec 02, 2011 | not rated yet | 0
- Imiquimod, an immune response modifier, is dependent on the OGF-OGFr signaling pathway Jul 24, 2008 | not rated yet | 0
- Scientists discover how cancers generate muscle-like contractions to spread around the body Aug 16, 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
Why is zone 1 in liver more prone to ischemic injury?
May 23, 2013 Hi, Is it because around central vein, there is only deoxygenated blood from the vein where as in the periphery there is hepatic artery. Also why...
How can there be villous adenoma in colon, if there are no villi there
May 22, 2013 As title suggest. Thanks :smile:
How can there be a term called "intestinal metaplasia" of stomach
May 21, 2013 Hello everyone, Ok Stomach's normal epithelium is simple columnar, now in intestinal type of adenocarcinoma of stomach it undergoes "intestinal...
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...
- More from Physics Forums - Medical Sciences
More news stories
In recent years, microRNAs (miRNAs) and other non-coding RNAs are small molecules that help control the expression of specific proteins. In recent years they have emerged as disease biomarkers. miRNA profiles have been used ...
Cancer 22 hours ago | not rated yet | 0
Cancer cells spread and grow by avoiding detection and destruction by the immune system. Stimulation of the immune system can help to eliminate cancer cells; however, there are many factors that cause the immune system to ...
Cancer 22 hours ago | 5 / 5 (1) | 0
Researchers from London's Kingston University have begun a two-year study which could help prolong the lives of people with colorectal tumours.
Cancer May 24, 2013 | 5 / 5 (1) | 0
Transformative research from Western University has identified new hormones in the body which may suppress breast cancer and stimulate the regression of breast tumors.
Cancer May 24, 2013 | 5 / 5 (2) | 0
(Medical Xpress)—Curtin University researchers have found evidence that targeting specific cells in the body can reverse the effects of cancer on the immune system.
Cancer May 24, 2013 | 5 / 5 (4) | 0
Coenzyme Q10 decreases all cause mortality by half, according to the results of a multicentre randomised double blind trial presented today at Heart Failure 2013 congress. It is the first drug to improve heart failure mortality ...
3 hours ago | not rated yet | 4
Women at a particular stage in their monthly menstrual cycle may be more vulnerable to some of the psychological side-effects associated with stressful experiences, according to a study from UCL.
22 hours ago | 3.7 / 5 (3) | 3 |
Heart failure accelerates the aging process and brings on early andropausal syndrome (AS), according to research presented today at the Heart Failure Congress 2013. AS, also referred to as male 'menopause', was four times ...
3 hours ago | not rated yet | 1
Two mutations central to the development of infantile myofibromatosis (IM)—a disorder characterized by multiple tumors involving the skin, bone, and soft tissue—may provide new therapeutic targets, according to researchers ...
19 hours ago | 3 / 5 (2) | 0 |
Biological processes are generally based on events at the molecular and cellular level. To understand what happens in the course of infections, diseases or normal bodily functions, scientists would need to ...
22 hours ago | 5 / 5 (5) | 0 |
(AP)—Department of Justice lawyers have again asked a federal appeals court in New York to delay lifting age restrictions and prescription requirements on an emergency contraceptive popularly known as the morning-after ...
3 hours ago | not rated yet | 0