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O Prêmio Nobel de Medicina foi concedido nesta segunda-feira (6/10) aos imunologistas Mary E. Brunkow e Fred Ramsdell, dos Estados Unidos, e ao japonês Shimon Sakaguchi, em reconhecimento às suas contribuições fundamentais para a imunologia.
Crédito: YouTube/Nobel Prize
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Crédito: YouTube/Nobel Prize
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NotíciasTranscrição
00:01Senhoras e senhores, bom dia e vocês são tão bem-vindos para o lançamento deste ano de Nobel Prize na Fysiola Euromédicina.
00:11Meu nome é Tomas Pärlman e eu sou o secretário-general da Nobel Assembleia.
00:17Eu vou primeiro ler o lançamento em Svédito, seguido em inglês.
00:22Eu vou então, como usual, apresentar algum background para o prize e abrir para perguntas.
00:33Nobelförsamlingen vid Karolinska institutet har idag beslutat att Nobelpriset i Fysiologi eller Medicin år 2025
00:42ska delas lika mellan Mary Brankov, Fred Ramstel och Shimon Sakaguchi
00:53för deras upptäckter rörande perifer immuntolerans.
00:58The Nobel Assembly at Karolinska institutet has today decided to award
01:04the 2025 Nobel Prize in Physiology or Medicine
01:09jointly to Mary Brankov, Fred Ramstel och Shimon Sakaguchi
01:15for their discoveries concerning peripheral immune tolerance.
01:20Here are the three laureates.
01:25Mary Brankov was born in 1961 and received a PhD from Princeton University in the United States.
01:34The work for which she is awarded was performed at a biotech company,
01:39Celltech Chiroscience in Bothell, Washington.
01:42She is currently a senior program manager at the Institute for Systems Biology in Seattle.
01:52Fred Ramstel was born in 1960 and received a PhD in 1987
01:58at the University of California in Los Angeles.
02:02The work for which he is awarded was performed at the same biotech company, Celltech Chiroscience.
02:09He is currently a scientific advisor at the company he himself founded,
02:16Sonoma Biotherapeutics in San Francisco and in Seattle.
02:23Shimon Sakaguchi was born in 1951, earned an MD in 1976
02:30and a PhD degree in 1983 from Kyoto University in Japan.
02:37The work for which he is awarded was initiated at ICHI Cancer Center Research Institute in Nagoya.
02:47He is currently a distinguished professor at the Immunology Frontier Research Center at Osaka University.
02:54I now turn to Professor Marie Varen Herlenius, member of the Nobel Committee,
03:04who will now describe this year's Nobel Prize discoveries.
03:09Please, Marie.
03:09This year's Nobel Prize in Physiology or Medicine relates to how we keep our immune system under control
03:30so we can fight all imaginable microbes and still avoid autoimmune disease.
03:37Let me explain.
03:39We are constantly exposed to a myriad microbes
03:44and our immune system has developed to protect us from them.
03:49To detect all different varieties of microbes,
03:53existing ones and ones that may come,
03:56specialized cells in our immune system, the T cells, have receptors.
04:01We can form billions and billions of these receptors,
04:05all with different shapes that bind to different proteins.
04:09The T cells help us fight infection,
04:13and without them we cannot live long.
04:17Among all this diversity,
04:20some T cells receptors will unavoidably recognize proteins and structures in our own bodies,
04:30so-called self-reactivity.
04:34These self-reactive T cells may become harmful
04:36and cause autoimmune diseases such as type 1 diabetes,
04:42multiple sclerosis, and rheumatoid arthritis.
04:45So, how does our body solve this problem?
04:51From early life, our T cells are generated in the bone marrow
04:55and then travel to the thymus, where they go through a test.
05:01In this test, harmful self-reactive T cells are eliminated in a process called central tolerance.
05:09For a long time, this was believed to be the only way self-tolerance is obtained.
05:17However, some self-reactive cells escape out into our circulation
05:23and are potentially dangerous.
05:26This year's Nobel Prize in Physiology or Medicine
05:30concerns the discovery of how those potentially harmful T cells are kept in check.
05:37The discovery started with Shimon Sakaguchi's interest in the phenomenon
05:44that removing the thymus from mice three days after birth
05:49led to an overreactive immune system which caused autoimmune diseases.
05:56However, if T cells from healthy mice were injected,
06:04the development of autoimmune disease was prevented.
06:09Sakaguchi realized that among these injected cells,
06:13there must be some cells that protect against the overreactive immune system
06:18and autoimmune diseases.
06:20He started a long search for these cells.
06:24Years later, he discovered that if the T cells to be transferred
06:30were depleted of cells with the cell surface protein CD25,
06:35this pool of cells would no longer protect against autoimmune diseases.
06:40But if the T cells with CD25 were also injected,
06:46the mice were protected.
06:47Sakaguchi called these CD25-positive cells regulatory T cells.
06:54Many researchers were, however, skeptical about the existence of regulatory T cells.
07:02The critical missing piece would come from Mary Branco and Fred Ramstel.
07:07They studied a mouse strain called scurphy because of its scaly skin.
07:14The scaly skin was part of the severe autoimmune disease the mice developed.
07:20Branco and Ramstel wanted to find the mutation causing the disease.
07:25Other researchers had shown that the scurphy mutation was somewhere in the middle of the X chromosome.
07:34Today, it's possible to map a mouse genome, the whole genome, in a few days,
07:39but at the time, it was an incredible challenge and like looking for a needle in a haystack.
07:46Branco and Ramstel still took on the enormous work of mapping the middle part of the X chromosome in detail
07:52and eventually established that the section of interest contained 20 potential genes.
07:59They then examined gene after gene.
08:03It was only with the 20th and last examined genes that they found the mutation.
08:10The faulty gene was previously unknown, but had many similarities with a group of genes called forkhead box or fox genes,
08:18and they named the new gene foxp3.
08:22Branco and Ramstel suspected that the rare autoimmune disease, IPEX,
08:29which is also linked to the X chromosome,
08:32could be the human variant of the scurphy mouse disease.
08:36To understand if that was the case,
08:39they analyzed samples from children with IPEX
08:42and found mutations in the foxp3 gene.
08:45These findings connected the foxp3 gene also to human autoimmune disease.
08:55These two key discoveries,
08:58Sakaguchi's identification of cells that regulate immune responses,
09:04and Branco's and Ramstel's identification of the foxp3 gene
09:08as important for keeping the immune system in control indicated that the foxp3 gene
09:15could be important for regulatory T cells.
09:18Shimon Sakaguchi was first to show that foxp3 is actually essential
09:25for the development of the regulatory T cells, so-called Tregs,
09:31and therefore critical in the peripheral immune tolerance.
09:36This was soon followed by reports from other scientists
09:39and unleashed a whole new field in immunology.
09:45Subsequent studies show that when autoreactive T cells get activated,
09:53the regulatory T cells act to control them,
09:57both through cell-cell contacts and by soluble molecules.
10:03In this way, immune tolerance can be maintained
10:06without deleting too many T cells
10:09which could be needed for our protection
10:12against current or future microbes.
10:17The discoveries have spurred development
10:21of several potential new treatments.
10:25Clinical trials are ongoing
10:27to increase the number of regulatory T cells
10:30for suppressing unwanted immune reactions
10:33in autoimmune disease or following organ transplantation.
10:36This is done either by injecting growth factors
10:40that stimulate regulatory T cells
10:43or by multiplying regulatory T cells in laboratories
10:46which can then be given to patients.
10:51The opposite approach is used in trials for cancer.
10:56Cancer cells can make use of our regulatory T cells
11:00to avoid immune reactions
11:04that could destroy the cancer cells.
11:07For cancer treatments, the focus is therefore
11:10on down-regulating or destroying the regulatory T cells
11:14so that our immune system can act
11:17against the malignant cells.
11:19To summarize, Mary Branco, Fred Ramsdell
11:27and Shimon Sakaguchi
11:28have provided fundamental knowledge
11:32of how the immune system is regulated
11:35and are therefore awarded this year's Nobel Prize
11:39in Physiology or Medicine
11:41for their discoveries concerning peripheral immune tolerance.
11:46Thank you, Mary.
11:53So, with that, I would like to open up for questions.
11:58So, please raise your hand
12:01and maybe say your name.
12:06Any question here?
12:07We have one question.
12:08Have you managed to reach one of the laureates today?
12:14Yeah, you said it exactly right.
12:17I was able to reach one of the laureates.
12:20And that was Shimon Sakaguchi, who I reached.
12:26I got hold of him at his lab
12:30and he sounded incredibly grateful
12:36and expressed that it was a fantastic honor.
12:40And he was quite taken by the news.
12:45Fortunately, I had a lot of information to give him,
12:47so that worked out okay.
12:49Unfortunately, I wasn't able to reach any of the other two.
12:52They are probably, we have their phone numbers,
12:55but they are probably on silent mode.
12:58And I asked them to, if they have a chance, call me back.
13:05Anyone else?
13:08Yes?
13:10Kör på.
13:15Could you please say something about concrete treatments
13:19that are based on this year's findings?
13:23Yeah.
13:24So, I'll give the word to,
13:27and I forgot to introduce also,
13:29we have two additional experts here.
13:32Gunilla Karlsson-Hedestam,
13:34member of the Nobel Committee,
13:36and also Olle Kämpe,
13:38chair of the Nobel Committee.
13:41And Olle, if you could take that first question.
13:45Yes.
13:47Sorry.
13:48What you have to realize is that
13:50this year's Nobel Laureate
13:52get the prize for discovering a principle,
13:56the principle where peripheral tolerance
13:59is mediated by key regulatory cells
14:03that are FOXP3 positive.
14:08So, having that said,
14:10there is quite a lot of development going on,
14:14but it's still early studies.
14:17which are both some negative studies
14:21and some studies that, in an early phase,
14:25has given positive results,
14:29like, for example,
14:30stimulating of the IL-2 receptor
14:34in patients with atopic dermatitis.
14:38So, the IL-2 receptor is the same as the CD25.
14:45And there is a lot of CD25 on T-regulatory cells,
14:50and then you can stimulate them,
14:51you expand them,
14:53and you get more T-regs.
14:55That's one study that has worked,
14:59but there are many more alternatives
15:02using genetic methods
15:09to insert specific T-cell receptors.
15:13if you know what the receptor
15:15against a specific autoantigen is,
15:19you can get much more forceful T-regulatory cells.
15:24Or you can use the CAR-T principle.
15:28You add genetically an antibody
15:31to the area where you want
15:33this suppression to occur.
15:37But as I said,
15:38we are in early days.
15:44Any more?
15:45Here we have one, yes.
15:46Hello, Bogdan Ratajewski
15:56from the Polish television.
15:58I wanted to ask,
15:58because as you mentioned,
16:00this year's prize,
16:01not unlike last year's,
16:03goes to what you would call
16:06fundamental research
16:08that furthers our understanding
16:10of what physiology and medicine
16:12and then later finds
16:14its practical applications.
16:16Why does the Nobel Committee
16:18decide to once again
16:20emphasize this area,
16:23this kind of research,
16:24as fundamental in science?
16:27Thank you very much.
16:28Maybe I could just briefly answer that.
16:33This is a prize in physiology or medicine.
16:36And as you say,
16:37I mean, they're tightly connected
16:39because physiology knowledge
16:40leads to medical treatments.
16:44And actually, as Ulle mentioned,
16:46there's a lot going on.
16:48There are currently over 200 clinical trials
16:51involving regulatory T cells.
16:54And it starts there.
16:55But you're absolutely right.
16:57This is a prize for a fundamental
16:59you discover and understanding.
17:02And it's a mix of that.
17:04We don't deliberately take a decision
17:07that this year it's going to be
17:09this or that.
17:10We always take the most suitable proposal
17:14that we have scrutinized
17:18and reviewed sufficiently.
17:21And that is really worthy of a Nobel Prize.
17:23Any more?
17:30I know people are usually eager
17:32for their interviews,
17:34but maybe you have something
17:36you're curious about
17:37that everyone else would be as well.
17:43No one?
17:44Doesn't seem so.
17:51And then we thank you very much for coming.
17:56And those of you who have planned interviews
18:00are welcome to find your location
18:03and we will help everyone
18:05as rapidly and fast as we can.
18:08Thank you so much.
18:09Thank you.
18:38Thank you.
19:08Thank you.
19:38Thank you.
20:08Thank you.
20:10Thank you.
20:38Thank you.
20:40Thank you.
20:42Thank you.
20:43Thank you.
20:44Thank you.
20:46Thank you.
20:47Thank you.
20:48Thank you.
20:50Thank you.
21:18Obrigado.
21:48Professor Rickard Sandberg, member of the Committee of the Nobel Prize in Physiology or Medicine,
22:16please tell me, what is this year's prize about?
22:19This year's prize is about how you keep our immune system in check.
22:24Basically, you know, our immune system is extremely powerful.
22:27We need to be able to fight off any possible microbe, even the ones we have never been exposed to before.
22:33At the same time, we need to not attack our own tissues and organs.
22:37And if we do, you know, we get autoimmune disorders.
22:40So this prize is about a new mechanism that keeps our immune system in check
22:45to only have his positive sides but try to remove the negative sides.
22:50Very exciting. How is this done then, this check?
22:55Yes, so our immune system, you know, they're born with, you know,
23:00combinatorial astronomical numbers of receptors or sensors you can think of
23:04that, you know, go around and check all the cells for infected microbes or, you know, pathological pieces.
23:10And in the first step, all of these immune cells or the T cells that we're talking about here,
23:15they go to the thymus, an organ, and they're all the ones that react on our own substances and structures.
23:22They are removed. But that is not enough.
23:25So many cells escape out into our bodies and there they can still self-react to our own organs and tissues.
23:33That's why we need this secondary mechanism, the regulatory T cells.
23:37So they are executing this function to check to make sure we are not attacking our own cells and tissues.
23:45And what could happen when we are attacking our own cells and tissues?
23:49Yes, exactly. So that leads to really, you know, unfortunate diseases.
23:53You know, examples are type 1 diabetes where, you know, insulin producing cells are attacked
23:58or in rheumatoid arthritis and many more autoimmune diseases.
24:02And, you know, one of the clues came from an autoimmune disease called IPEX, which is much more rare.
24:07But if you have a mutation in a particular gene, you develop very acute autoimmune disorders
24:13and you have, you know, a full spectrum of disease manifestations like chronic diarrhea
24:18or eczema on the skin and type 1 diabetes stages.
24:24And why are you, why is this price so important, would you say?
24:30I mean, it opens a completely new dimension, sort of, how to think about this important immune system balance check,
24:38sort of, how to keep them in check while still having this broad repertoire.
24:42And by knowing about the existence of these regulatory T cells, we also have the ability to start thinking about
24:48how can we increase their activity or decrease their activity.
24:51So, for example, in autoimmune disorders, you know, where they're not having sufficient suppressive effect,
24:57we would like to boost their function or the numbers.
25:00And, you know, by this knowledge, we have new ideas to explore.
25:04And, you know, there's, you know, early stages and it takes a long while to develop new therapeutics.
25:08But, of course, we have a new handle on how to attack these problems.
25:12And how could this, in the future, affect our daily lives?
25:17Yeah, so, I mean, hopefully these approaches will be effective in order to, you know, stimulate these T cells,
25:24the regulatory T cells, to help you suppress autoimmune disorders.
25:28Or maybe make organ transplantation less problematic by, you know, dampening the immune system's ability to project the new organ.
25:38And also in cancer, it's being explored if one can, you know, remove their suppressive ability to make it easier for immune cells to attack cancer cells.
25:47In the future?
25:48In the future, exactly. But there are over 200 clinical tests ongoing, so there's just a lot of activity.
25:53But, of course, it's a long road to travel.
25:55So, what about the laureates, these three laureates? Could you tell us something about them?
25:59Yeah, so, I don't know them personally. I don't think I actually have ever met any of those three.
26:05But, I mean, Shimon Sakaguchi, of course, is a very large figure in the immunological sciences,
26:13and, you know, has been following this rich tradition of Japanese immunologists.
26:19Whereas, I think, the other two laureates are perhaps more surprised by being awarded this prize for their very important contributions.
26:27But they also work in another, you know, one of them work in the biotech sector,
26:31and the other one has had a career also that is maybe not a typical academic professor career.
26:37So, what kind of careers do they have that surprises us, would you say?
26:41No, but they've made their discoveries in, you know, over 20 years ago in a biotech company already,
26:46and they have had different career paths from there on.
26:49But, you know, the important thing is to make a breakthrough discovery, not in the context of how you're doing it, of course.
26:56Finally, if you would tell me in 30 seconds why you are so excited about this year's prize, what would that be?
27:08I mean, it's a fundamental discovery about the principle that sort of keeps our immune system in check.
27:14Very important for not having us all develop autoimmune disorders.
27:18So, that is the reason for me.
27:22Thank you so much, Professor Rickard Salén.
27:25Samberg.
27:26Samberg.
27:27Member of the Committee of the Nobel Prize in Physiology or Medicine.
27:30Thank you so much.
27:31Samberg.
27:32Samberg.
27:33Samberg.
27:34Samberg.
27:35Samberg.
27:36Samberg.
27:37Samberg.
27:38Samberg.
27:39Samberg.
27:40Samberg.
27:41Samberg.
27:42Samberg.
27:43Samberg.
27:44Samberg.
27:45Samberg.
27:46Samberg.
27:48Samberg.
27:49Samberg.
28:18E aí
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