James Webb hunts for a haze-less exoplanet to answer longstanding mystery
Smaller than ice giants like Neptune or Uranus but with a gas composition more similar to Saturn or Juputer, Sub-Neptunes are thought to be the most common type of exoplanet, but they are hard to study because they are typically obscured by clouds and haze. That means that astronomers haven't been able to study their atmospheres, or to learn much about how these planets evolve, or why we don't have one in our solar system.
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But recently, astronomers were able to use Webb to study a sub-Neptune called TOI-421 b. 'I had been waiting my entire career for Webb so that we could meaningfully characterize the atmospheres of these smaller planets,' said lead researcher Eliza Kempton of the University of Maryland, College Park. 'By studying their atmospheres, we're getting a better understanding of how sub-Neptunes formed and evolved, and part of that is understanding why they don't exist in our solar system.'
This particular planet was selected for study because of its extreme heat, with a scorching temperature of around 1,340 degrees Fahrenheit. That is high enough there shouldn't be methane present in the planet's atmosphere, which means that it shouldn't form a haze — and should therefore be easier to observe.
'Why did we observe this planet, TOI-421 b? It's because we thought that maybe it wouldn't have hazes,' said Kempton. 'And the reason is that there were some previous data that implied that maybe planets over a certain temperature range were less enshrouded by haze or clouds than others.'
Thanks to the lack of haze, the researchers were able to look into the planet's atmosphere and see what it was composed of. They found water vapor, with a large amount of hydrogen in the atmosphere, as well as suggestions of carbon monoxide and sulfur dioxide — but notably, no indications of methane or carbon dioxide. The large amount of hydrogen was a surprise as it differs from the few other sub-Neptunes that have been observed with Webb — so could this planet be an anomaly? Or perhaps it formed in a different way from these other similar planets?
The researchers hope to observe more sub-Neptunes to find out. 'We've unlocked a new way to look at these sub-Neptunes,' said researcher Brian Davenport. 'These high-temperature planets are amenable to characterization. So by looking at sub-Neptunes of this temperature, we're perhaps more likely to accelerate our ability to learn about these planets.'
The research is published in The Astrophysical Journal Letters.
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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. 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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. 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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.
