Traders trimmed wagers on the European Central Bank delivering another interest-rate reduction by the end of the year, after President Christine Lagarde indicated officials have scope to pause their cutting cycle.
Money markets now show a 70% probability of a quarter-point cut, compared with about 90% before Thursday’s monetary policy decision. The ECB kept interest rates unchanged for the first time in more than a year as predicted by a majority of economists.
This transcript has been edited for clarity.
Welcome, everybody. My name is Teresa Amaral. Today I’m here with you to follow up on my presentation on the best of ASCO 2025. Today, we’ll have two different sections. The first one is dedicated to the rapid oral communications, and the second one is dedicated to the oral communications that took place on the last day of the congress.
For the rapid oral communications, we’ll focus on one topic that came through three presentations, tumor-infiltrating lymphocyte (TIL) therapy. Then we will look into a very interesting aspect: the reduction in toxicity associated with immunotherapy that we know is an important aspect for patients that need to receive immunotherapy. And finally, we’ll look into a potential modifiable factor that might be associated with better outcomes in patients receiving immunotherapy, which is a diet rich in fiber.
In the oral communications, we’ll focus on the adjuvant trials — two of them that were quite important to be presented in this session. Then [I’ll discuss] a trial that dealt with an unanswered question, which is how long should we treat patients in the metastatic setting. And finally, we will look into two different trials. The first one was on sequencing therapy, which was the DREAMseq trial on the final analysis, and then [there was] a specific analysis for patients that have symptomatic brain metastases, which are still a population of patients that unfortunately are excluded from the majority of clinical trials despite the fact that they do not a very good outcome.
Starting with the TIL therapy, the first trial or the first presentation that I want to show you is a new way of applying TIL therapy. Basically, this is a new engineered TIL cell therapy that is intended to be given to patients that already received immune checkpoint inhibitors — so [patients] that are resistant to this therapy. But the interesting part of this type of therapy is that it doesn’t require giving interleukin-2, and it also is possible to be given with a low dose of lymphodepletion. This is one of the reasons why I decided to bring this study because we know that TIL therapy might have a good outcome in the long run and these are the results that we are going to discuss in the next presentation.
One of the problems is the toxicity that is associated with the pre-therapy and the after-therapy that we need to give to these patients, which includes this lymphodepleting chemotherapy and then the interleukin-2. What these very preliminary data showed is that it is indeed feasible to do this type of therapy by not giving interleukin-2 and reducing the lymphodepleting chemotherapy, and that the overall response rate was quite reassuring because we have an overall response rate that is around 67%. The median duration of response was not reached.
Of course, we will need to wait for further data because this phase 1/2 trial is recruiting and we will need to confirm this data further in a broader population with more patients. But I think these results are quite reassuring and will maybe allow us to give this type of therapy to a broader spectrum of patients, as we don’t need to have fitter patients to receive this therapy because we have low toxicity.
The next discussion, or the next work, that was presented was indeed quite interesting because it looked into the 5-year-old outcome of another TIL product that is called lifileucel. Basically, what the authors showed was that this one-time therapy that was given was able to demonstrate durable and deepening responses in patients with advanced melanoma.
It was also interesting to see the long-term toxicity is not more than what we saw before, because the toxicity is mostly associated with the interleukin-2 and lymphodepleting chemotherapy that is necessary to give with this product. So in line with what we discussed in the previous work, this is one of the reasons why most patients, or some patients, cannot receive this type of therapy.
What we saw was that after 5 years, approximately 20% of the patients remained alive. Obviously, the best outcomes are seen in the patients that do respond. If the patient responds, the chances that they have a long-term outcome are significant, which is expected. So, the other side shows that this might be feasible, at least for approximately one fifth of the population.
Another point that I would like to go through with you is that we saw two works looking into TILs that are definitely a potential therapeutic option for patients that received therapy in the first line, or patients that did not benefit from immunotherapy in the first line.
The third work that I would like to discuss with you is the fact — and it was also presented in these rapid oral communications — that indeed not all TILs that we give to patients are the same. What the authors from this work looked into are the infusion product characteristics that are able to predict the response of patients that are treated with TILs. What they showed is the TIL persistence and also the distinctive TIL population in terms of immunophenotypic features, in terms of the proportion of CD8+ T cells, and the high surface expression of LAG3+.
All of these characteristics are associated with improved TIL outcomes in patients with metastatic melanoma, meaning that not everything that we infuse that are called TILs work exactly the same and have the same influence, let’s say, on the patient’s response. This is obviously important because in the future, we might need to concentrate on some strategies, or on other strategies, that modulate ex vivoTIL expansion, so that we have the optimal TIL phenotype associated with better outcomes and we make sure the TILs that we are giving to our patients are the ones that will most likely produce a better outcome — a longer response, but a more durable response. I found this work quite interesting because it’s always nice and important to look into these details and understand exactly what we are treating our patients with and how these treatment characteristics influence the patient’s outcomes.
The second point I would like to discuss with you is the toxicity that I mentioned in the very beginning. We treat a significant amount of patients with immunotherapy, but we know that one of the problems of immunotherapy is the toxicity associated with the therapy. Several strategies are being investigated to reduce the toxicity associated with immunotherapy. One of the strategies that was presented this year is looking into interleukin-6 receptor blocking with an antibody called sarilumab. This was tested in patients that received a combination of ipilimumab, nivolumab, and relatlimab — patients with resectable stage III or stage IV melanoma.
Basically, what the author showed was that indeed it was possible to reduce the toxicity associated with this triple combination. Not only did this reduce the grade 3 to grade 5 immune-related adverse events to 12% when we use this interleukin-6 receptor inhibitor, but it also resulted in the best overall response rate being more than 60% — 64%, approximately.
This means that it might not only be able to reduce the severe toxicity, so grade 3 and grade 4 adverse events, but also allow patients to have a long-term benefit — especially because this is one of the highest overall response rates that we saw recently in terms of combination of immunotherapy. Obviously, these data need to be confirmed by a larger trial looking into whether this triple combination with, or without, this interleukin-6 receptor inhibitor allows lower toxicity and the high response rate we saw in this smaller trial.
Finally, for the rapid oral communications, I would like to show you a trial that looks into acting on some potential modulated factors, including the diet of the patients that we treat with immune checkpoint inhibitors. This was a randomized phase 2 trial that looked into a high-fiber diet intervention in patients who received immune checkpoint inhibitors. What they showed is that it is feasible to do these kinds of studies, but it’s quite challenging, especially because some patients progressed earlier or abandoned the study due to other aspects that did not really have to do with the diet itself. Giving this high-fiber diet is safe and it’s also well tolerated, and it seems that this high-fiber diet might lead to improved responses in patients receiving immune checkpoint inhibitors.
I must say that it might lead [to these responses], only because these are very preliminary data and they need some kind of confirmation before we start prescribing high fiber diets to all patients that are receiving immune checkpoint inhibitors. I think it’s very interesting that these types of factors are being analyzed and are being discussed and investigated because these might be, I would say, simple changes that we can make in order to improve the patient’s outcomes to the current therapies that we offer them anyhow.
Moving into oral communications, I will start by looking into the adjuvant trials. Two important adjuvant trials were discussed. The first one was RELATIVITY-098. This was a trial that investigated programmed cell death protein 1 (PD-1) monotherapy vs PD-1 plus a LAG-3 inhibitor in the adjuvant setting. Unfortunately, the trial was negative, but I think it’s very important that we show these negative trials because it allows us to understand what happened and prevents other companies or other groups from looking at the same question exactly the same way, because the reasons, or the potential reasons, for the failure of the trial were not known or were not published. I think it’s very important that these negative data are presented so that we can all learn and avoid repetition of the same issues. Basically, the combination did not improve relapse-free survival compared to the monotherapy, although there were no new safety data.
Interestingly enough, from the biomarker analysis and the preliminary analysis that was presented, the message came out that for this combination to work, it may be necessary for some tumor cells to be present and not completely excised, as was [the case] in this setting. These comparisons were made with the same combination in the metastatic setting, where the combination was better than immunotherapy. This kind of analysis is always interesting to look into because it might give us some hints on where we can move with this combination in the future.
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I interviewed Ozzy in 1997, for Kerrang! magazine. We met in a hotel on the Champs-Élysées in Paris, where he proceeded to drink gallons of Diet Coke, and take the piss out of himself. He was the least pretentious rock star I ever met, and during my decade in the industry, I met hundreds.
By the time I met Ozzy, I’d had enough of music journalism. I decided he should be my final interview because how do you beat that? I’d interviewed everyone I’d ever wanted to, including Nirvana, so it made sense to end my music journalism career by chatting with Ozzy.
Ozzy was so self-effacing and hilarious. He told me about becoming partially deaf while working in a factory testing car horns, how he’d thought Spinal Tap was a documentary about Black Sabbath, and how the band named themselves after a horror movie for a joke. He was already shaking back then, and seemed very small and frail, but he had this gorgeous twinkling quality, which I certainly hadn’t expected to encounter in the Prince of Darkness. And he clearly couldn’t do a thing without Sharon, which he was more than happy to admit. Liz Evans, Tasmania, Australia
My first ever gig was Ozzfest 2002 at Donington. I was so excited, I dyed my hair black and carried a wallet chain thick enough to tie up a ship. When I arrived, a guy in a top hat with a voice like the devil said I’d be “lucky if I made it out alive”. I’d largely wanted to go because of System of a Down. But Ozzy was the show stealer. I’d become familiar with him due to the The Osbournes, then got into Black Sabbath. There was no other performer like him over the weekend. This – what I thought at the time – old guy had more energy than the younger bands put together. Needless to say, I was hooked on metal from that point onwards. Because of that festival so many bands got their big breaks. He not only invented metal with Sabbath but continued to support the genre the rest of his days. James, Cambridge
I was a fairly obsessive heavy rock fan in my teens, and first saw Ozzy live when I was 16 at a one-day heavy metal festival at Port Vale’s football ground in Stoke-on-Trent in 1981, alongside a few other bands including Motörhead. A couple of years later I was at university in Sheffield, and saw him for a second time at the City Hall. Afterwards, a friend and I got tipped off about which hotel the band were staying in, so we gatecrashed the residents-only bar and ended up spending an hour or two in the company of Ozzy, Sharon, and the rest of the band. He was an absolute gentleman, happily putting up with a bunch of geeky 18-year-old fans asking him loads of questions, and he insisted on buying multiple rounds of drinks for everyone in the bar. Before we departed he also decided to sign our foreheads “Ozzy was here” with a Sharpie, as per the photo – earning us a huge amount of credibility when we finally got back to our hall of residence. What an absolute legend of a man – definitely one of a kind. Nick Payne, St Albans
As teenagers in the early 1980s we all used to go to venues early and hang around the loading areas and back-stage entrances, on the off-chance of picking up an autograph or seeing a rock star. We did so during the Blizzard of Ozz tour, which were his first UK appearances since being sacked from Sabbath. We got there very early, around 2pm, and turned the corner to find guitarist Randy Rhoads and Ozzy himself, sat quietly having a cup of tea. We gathered tentatively and joined him.
Rhoads and Ozzy gave off an air of openness and gentle bonhomie. This wasn’t the Prince of Darkness, but a slightly apprehensive man who was hoping that the fans would accept his new musical incarnation. He was humble, communicative and very patient. It was like sitting with a mate’s older brother, shooting the breeze for 20 minutes. After he and Randy went back in to sound check, we all remained stunned for a few moments. We’d had a cup of tea with the Prince of Darkness, and it turned out he was a really nice bloke. It’s a real shame that successive generations only know him as the sometimes incoherent, grumpy old man of the TV show, The Osbournes. As in his heyday, he was the funniest and most disarming of all of the 1980s rock gods. Van Norris, Hampshire
I was lucky enough to see Black Sabbath at Download festival in 2012. Ozzy was already a huge legend but hadn’t done a show in a while and we went genuinely thinking that it may be the last chance to see him. When he wobbled out on to the stage, clearly a bit frail, I was worried. Oh no, I thought, this is a cash grab and he’s really not up to it anymore … but then he opened his mouth, and wow. His voice was still all there – it was like listening to him in his heyday. I’m still agog at how good he was. And he was clearly enjoying himself immensely. We’ve lost a great. Coral Pearce-Mariner, Norfolk
In February 1972, during the Master of Reality tour, my father was due to pick me and my mates up after the gig at De Montfort Hall in Leicester, but was delayed by the bad weather. We hung round the back stage door and eventually the band came out. We spoke to all of them but it was Ozzy and Bill who gave us the most time. Ozzy threw the first snowball at us. We then had an amazing snowball fight with Ozzy and Bill which seemed to go on for ages. Ozzy, laughing and out of breath, thanked us for the fight and left with Bill covered in snow. For four kids from a small rural town it was magical. The gig was incredible. Gazza, Leicester
I saw Ozzy when I was 17, at one of the very first gigs they played as Black Sabbath, at a mini festival organised by the Midlands Arts Centre for Young People in Cannon Hill Park, Birmingham, on bank holiday Monday, 1 September 1969. They’d originally been billed as Earth, but by the time they went on stage, they had become Black Sabbath. Rumours abounded that they had played at a school dance at the Convent of the Holy Child Jesus school in Edgbaston, where they had performed with a huge inverted crucifix on the stage behind them, much to the outrage of the nuns who ran the school. Because we knew most of the security crew at the festival, we watched them from backstage. Though they didn’t have top billing, it was clear even then that they were the best band on stage that day, and that Ozzy had incredible charisma.
That autumn, before they became nationally famous, I remember they occasionally used to turn up in the coffee bar at the arts centre where I and my friends hung out. Did I ever dare to speak to the Prince of Darkness? I doubt it, but he might once have asked me for a light … When their first album came out the following year, I decided to model my own look on the spooky proto-Goth lady, dressed all in black, on the front cover. To my mind, that’s still their best album, and I have it still; it sums up for me the cusp between the 60s and the 70s, and the awkward but euphoric liminal space between my adolescence and adulthood. Jenni Mills, Wiltshire
The importance and significance of both Ozzy and Sabbath only truly sunk into my brain during the Back to the Beginning gig on 5 July, which I saw on live stream. It was a wonderful day seeing so many of my favourite bands pay tribute. The nail was finally hit on the head seeing Ozzy at the end. Some members of the crowd were in tears to see him performing well despite his physical deterioration. I wasn’t sad for him at all – he looked like he was having the time of his life. I’ve also seen plenty of Ozzy live and am blown away by his stage persona. Thanks for everything, oh Prince of Darkness! George Heron, Liverpool
The Pakistan hockey team’s participation in the 2025-26 FIH Pro League lies in jeopardy because of financial crunch, derailing the three-time Olympic champions’ much-anticipated comeback at the international stage.
The Pakistan men’s hockey team, which has won the World Cup four times, has been invited to compete in the FIH Pro League 2025-26 after New Zealand, which had earned direct qualification by winning the 2024-25 Nations Cup, decided not to participate in the upcoming season.
The International Hockey Federation (FIH), the game’s governing body, formally extended the invitation to Pakistan on Wednesday and had given them a deadline till August 12 to inform their confirmation. Pakistan, which has failed to qualify for the last three Olympics and also World Cup, has been given an opportunity by the FIH to compete against top tier teams Argentina, Australia, Belgium, England, Germany, India, Netherlands and Spain in the competition that will be held from December, 2025 till June, 2026.
But the problem is that the cash-strapped Pakistan Hockey Federation (PHF) doesn’t have funds to send the team for the Pro League.
The PHF have now requested the Pakistan Sports Board (PSB) to release 700 million rupees (around USD 2.5 million) for the entire campaign.
The state run PSB, at its recent annual meeting, made it clear that it doesn’t have the funds to ensure Pakistan’s participation in the Pro League.
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The PSB, in fact, has already directed the PHF to submit detailed accounts of the funds allocated to them since last year and have flatly refused to release more funds to the national federation to pay daily and travel allowances of players and officials, who went to the recent FIH Nations Cup.
Pakistan lost in the final of the FIH Nations Cup to New Zealand, who automatically qualified for the Pro League.
But New Zealand have informed the FIH that they wouldn’t be sending their team, as a result of which second-best Pakistan have got a chance to compete against the top tier teams.
“But whether this will be possible has to be seen as the PSB will send a summary to the Prime Minister for allocation of special funds to allow the PHF to send the team to the Pro League,” an official in the PSB said.
He made it clear that because of the failure of the PHF to update the PSB on how they had spent funds released to them since last year the Prime Minister, who is patron-in-chief of the PHF might opt for a change in the top leadership of the federation before approving special funds of 700 million rupees.
Rasheedul Hassan, an Olympic gold medallist who has launched a campaign against the PHF, said unfortunately the officials who had managed the federation affairs for last many years had failed to keep a clean image.
When the inaugural Pro League was held, the PHF had initially confirmed participation in the event but later backed out citing lack of funds as a result it ended up paying a fine of 170,000 euros to the FIH.
For record, Pakistan is the most successful national team in the Asian Games history, with eight gold medals — 1958, 1962, 1970, 1974, 1978, 1982, 1990, and 2010, the highest number of times a country has become Asian Champion.
Pakistan is also the only Asian team to have won the prestigious Champions Trophy thrice — 1978, 1980 and 1994.
image:
Bathylepeta wadatsumi and “Large Monk” Wadatsumi.
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Credit: Limpet photograph: Chen et al.; Illustration: ONE PIECE (TV series) Toei Animation.
Researchers from Japan Agency for Marine-Earth Science and Technology (JAMSTEC) have discovered a deep-sea limpet species 5,922 metres beneath the northwestern Pacific Ocean, marking the deepest known habitat for any true limpet (subclass Patellogastropoda).
Described as a new species in the open-access journal Zoosystematics and Evolution, the limpet was found on hard volcanic rock 500 kilometres southeast of Tokyo, Japan. The gastropod measures up to 40.5 mm in shell length, a remarkably large size for a true limpet from such depths.
The new species was named Bathylepeta wadatsumi, a reference to Wadatsumi, the god of the sea in Japanese mythology, and the character “Large Monk” Wadatsumi, from the manga series ONE PIECE. The character’s enormous size mirrors that of the newly discovered limpet.
The researchers behind the discovery paid further homage to the world’s most popular manga series in their acknowledgements, writing:
“We also take this opportunity to salute Eiichiro Oda for continuing to chart the epic voyage of ONE PIECE (1997–), which reminds us that the greatest voyages are driven by freedom, camaraderie, and an insatiable thirst for discovery.”
The new species was collected using the crewed submersible DSV Shinkai 6500, making it the first time a member of the genus Bathylepeta has been observed and photographed live on its natural rocky substrate, rather than being dredged using a net. The use of submersibles is instrumental in accessing these habitats, allowing for direct observation and collection of previously overlooked organisms.
Dr. Chong Chen, lead author of the research paper, said: “Even in an age of sophisticated remotely operated vehicles, there’s often an edge to the human eye on the seafloor. Crewed submersibles like Shinkai 6500 let us explore with intention and nuance—spotting lifeforms like Bathylepeta wadatsumi that might otherwise be missed entirely.”
Beyond its taxonomic significance, the study has broader ecological implications as B. wadatsumi appears to graze on sediment layers over rock, indicating a specialised role in processing organic matter in deep-sea ecosystems.
The findings underscore the need for more comprehensive explorations of rocky abyssal habitats using submersibles to reveal the true diversity and distribution of Bathylepeta and other animals relying on such habitats.
Original source
Chen C, Tsuda M, Ishitani Y (2025) A new large-sized lepetid limpet from the abyssal northwestern Pacific is the deepest known patellogastropod. Zoosystematics and Evolution 101(3): 1249-1058. https://doi.org/10.3897/zse.101.156207
Zoosystematics and Evolution
24-Jul-2025
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