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	<title>ICOS &#8211; Science</title>
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	<title>ICOS &#8211; Science</title>
	<link>https://scienmag.com</link>
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		<title>Cows, Canopies and Climate: Why a Few Metres of Height Matter for Europe&#8217;s Longest CO2 Record</title>
		<link>https://scienmag.com/cows-canopies-and-climate-why-a-few-metres-of-height-matter-for-europes-longest-co2-record/</link>
		
		<dc:creator><![CDATA[Russell Cooper]]></dc:creator>
		<pubDate>Wed, 14 Oct 2026 12:40:50 +0000</pubDate>
				<category><![CDATA[Athmospheric]]></category>
		<category><![CDATA[Technology and Engineering]]></category>
		<category><![CDATA[atmospheric greenhouse gases]]></category>
		<category><![CDATA[atmospheric methane tracking]]></category>
		<category><![CDATA[Black Forest]]></category>
		<category><![CDATA[carbon dioxide]]></category>
		<category><![CDATA[cavity ringdown spectroscopy]]></category>
		<category><![CDATA[Climate change monitoring]]></category>
		<category><![CDATA[climate data consistency and accuracy]]></category>
		<category><![CDATA[diurnal cycle]]></category>
		<category><![CDATA[environmental research on atmospheric sampling]]></category>
		<category><![CDATA[European CO2 records]]></category>
		<category><![CDATA[greenhouse gas monitoring]]></category>
		<category><![CDATA[high-altitude air quality measurement]]></category>
		<category><![CDATA[ICOS]]></category>
		<category><![CDATA[ICOS European monitoring network]]></category>
		<category><![CDATA[impact of measurement height on climate data]]></category>
		<category><![CDATA[intake height]]></category>
		<category><![CDATA[long-term climate data]]></category>
		<category><![CDATA[long-term time series]]></category>
		<category><![CDATA[methane]]></category>
		<category><![CDATA[mountain station CO2 measurement]]></category>
		<category><![CDATA[REBS spike detection]]></category>
		<category><![CDATA[Schauinsland station]]></category>
		<category><![CDATA[seasonal CO2 variations in Europe]]></category>
		<category><![CDATA[seasonal cycle]]></category>
		<guid isPermaLink="false">https://scienmag.com/?p=270907</guid>

					<description><![CDATA[A three-year comparison at Germany's Schauinsland station shows that moving a greenhouse gas air intake from 12 to 35 metres systematically alters summer CO2 readings while escaping methane spikes from nearby grazing cows.]]></description>
										<content:encoded><![CDATA[<p>High on a ridge in Germany&#8217;s Black Forest, one of the most important climate records in Europe hangs on a technical question of just 23 metres. Schauinsland station, perched roughly 1,000 metres above the densely populated Rhine Valley, has been measuring atmospheric carbon dioxide continuously since 1972, making it the longest-running CO2 time series on the continent. Methane measurements followed in 1991. Now, a team of researchers from Heidelberg University and the German Environment Agency has carried out a meticulous three-year experiment to answer a deceptively simple question: if the station&#8217;s air intake were moved from 12 metres above the ground to 35 metres, would the record still mean the same thing? The answer, published in Atmospheric Measurement Techniques, is a nuanced one, and it matters far beyond one mountaintop.</p>
<p>The stakes are higher than they might appear. Greenhouse gas monitoring networks such as the European Integrated Carbon Observation System, or ICOS, and the World Meteorological Organization&#8217;s Global Atmosphere Watch programme demand extraordinary measurement consistency. Compatibility targets are set at 0.1 parts per million for CO2 and 2 parts per billion for methane, because the seasonal differences in CO2 between European stations typically amount to only a few parts per million. Even the severe drought and heatwave that struck Central Europe in the summer of 2018 perturbed seasonal CO2 cycles by just 1.4 parts per million in the hardest-hit regions. Against that backdrop, a systematic bias of half a part per million introduced by a change in intake height would be far from trivial. It could ripple through the inverse models that scientists use to estimate how much carbon Europe&#8217;s forests, soils and industries emit and absorb.</p>
<p>The motivation for the study was practical. In September 2021, a new air intake line was installed on a radio tower about 50 metres from the station, at 35 metres above ground level, alongside the routine 12-metre inlet that has served the site since 2005. The higher intake was intended to reduce the influence of local surface fluxes, the breath of the surrounding meadows and forests that can contaminate what is supposed to be a regional background signal. To find out whether the two heights told the same story, the researchers equipped each intake with its own Cavity Ringdown Spectroscopy analyzer, allowing truly simultaneous measurements of CO2, methane and water vapour at a temporal resolution of 3.6 seconds. Air from the tower travels down a SynFlex tube, is pre-dried at 2 degrees Celsius, and reaches its analyzer after roughly a minute of transit, a delay the team carefully corrected for.</p>
<p>Before comparing the air itself, the team had to prove the instruments agreed with each other. Following the ICOS calibration protocol, both analyzers were tied to the WMO X2019 CO2 and X2004A methane scales through four calibration cylinders, with regular injections of short-term and long-term target gases treated as unknown samples. The results were reassuring: the mean difference between the two analyzers was 0.014 parts per million for CO2 and a negligible fraction of a part per billion for methane, comfortably within the WMO compatibility goals. Any differences between the two intake heights could therefore be attributed to the atmosphere, not the hardware. With that foundation, the researchers aggregated three full years of parallel data, from 2022 to 2024, into diurnal and seasonal cycles for each intake height.</p>
<p>The CO2 results revealed a striking seasonal asymmetry. In winter, when the surrounding biosphere is dormant, the two intake heights agreed almost perfectly, with differences remaining below plus or minus 0.1 parts per million throughout the day. Summer was another matter entirely. During daylight hours, mean CO2 at 35 metres ran up to 0.5 parts per million higher than at 12 metres, because photosynthesis in the nearby vegetation actively draws down CO2 near the surface, depleting the air sampled by the lower intake. At night the pattern reversed: respiration from soil and plants released CO2 that accumulated near the ground, pushing 12-metre values up to 1.1 parts per million above the 35-metre record. The result was a diurnal amplitude of 5.0 parts per million at 12 metres in summer, versus only 3.9 parts per million at 35 metres. Monthly summer means were on average 0.26 parts per million higher at 12 metres, peaking at 0.56 parts per million.</p>
<p>These numbers are small in absolute terms but large relative to the signals scientists hunt for. The diurnal CO2 cycle carries the imprint of biospheric fluxes, and misrepresenting it can introduce substantial bias in flux inversions at continental and regional scales. The findings also raise an uncomfortable possibility: the vertical gradient the team measured suggests that local biospheric fluxes may have influenced the historic 12-metre record to a non-negligible degree, particularly as vegetation and climate conditions have shifted over recent decades. With the station&#8217;s measurement equipment moving to a new building nearby in 2025, the 35-metre record now serves as a stable reference for bridging any discontinuity in the five-decade CO2 series, and complementary eddy covariance measurements using the tower could yield fresh insight into the local biosphere at modest cost.</p>
<p>Methane told a very different story, at least on average. Diurnal and seasonal mean differences between the two heights stayed below plus or minus 1.2 parts per billion, well within compatibility goals, meaning the 35-metre record can extend the historic methane time series without a significant break. But the minute-by-minute data exposed a charmingly rural culprit. During the grazing season from May to November, cows on the meadows surrounding the station, some just a few dozen metres from the intakes, produced sharp methane spikes reaching up to 369 parts per billion in minutely data and 38 parts per billion in hourly means at 12 metres. The 35-metre intake, by contrast, remained largely untouched by the bovine emissions. Differences larger than 20 parts per billion appeared three to fourteen times more often during the grazing season than in winter, and the spikes clustered during daytime hours and in air arriving from the west-southwest, where the largest meadows lie.</p>
<p>Filtering out these spikes proved harder than detecting them. Manual flagging was impractical given the sheer frequency of events, and a standard-deviation-based algorithm retained too much contaminated data. The researchers instead turned to the Robust Extraction of Baseline Signal algorithm, or REBS, which models a slowly varying baseline and flags points exceeding it by a tunable threshold. With a 60-minute bandwidth and a stringent threshold parameter of 3, REBS identified 7.9 percent of minutely grazing-season data as spikes, reducing hourly means by up to 27 parts per billion. Yet even this approach struggled during intense spiking periods, when the baseline itself was dragged upward, and the stringent setting tended to over-detect on clean days. Over the full three years, 3.4 percent of hourly values deviated from the original record by more than 2 parts per billion after filtering, and monthly means shifted by up to 1.8 parts per billion, enough to matter for model comparisons.</p>
<p>The team&#8217;s recommendation is pragmatic: keep measuring at both heights. The 12-metre inlet preserves continuity with the historical CO2 record spanning more than five decades, while the 35-metre data provide an essential reference for detecting bias, and the cleaner methane record at 35 metres should anchor future analysis. For the historic 12-metre methane data, applying spike detection during the grazing season, with human oversight, could remove a subtle but real contamination. In an era when the European land carbon sink appears to be weakening under heat and drought, and when every tenth of a part per million shapes our understanding of who emits and who absorbs, the Schauinsland study is a reminder that climate science sometimes turns on the finest of margins, and that even cows deserve a footnote in the global carbon budget.</p>
<p><strong>Subject of Research:</strong> Comparative analysis of atmospheric CO2 and CH4 measurements at 12 m and 35 m intake heights at the Schauinsland long-term monitoring station in Germany</p>
<p><strong>Article Title:</strong> Atmospheric CO2 and CH4 measurements at Schauinsland station, Germany: a comparative study of diurnal and seasonal variations at 12 and 35 m intake height</p>
<p><strong>Article References:</strong> Großmann, J., Meinhardt, F., Hoheisel, A., Hellack, B., &amp; Schmidt, M. (2026). Atmospheric CO 2 and CH 4 measurements at Schauinsland station, Germany: a comparative study of diurnal and seasonal variations at 12 and 35 m intake height. <em>Atmospheric Measurement Techniques, 19</em>(19), 6469-6485. <a href="https://doi.org/10.5194/amt-19-6469-2026" rel="noopener noreferrer">https://doi.org/10.5194/amt-19-6469-2026</a></p>
<p><strong>Image Credits:</strong> AI Generated</p>
<p><strong>DOI:</strong> <a href="https://doi.org/10.5194/amt-19-6469-2026" rel="noopener noreferrer">10.5194/amt-19-6469-2026</a></p>
<p><strong>Keywords:</strong> Schauinsland station, carbon dioxide, methane, greenhouse gas monitoring, ICOS, intake height, diurnal cycle, seasonal cycle, cavity ringdown spectroscopy, REBS spike detection, Black Forest, long-term time series</p>
]]></content:encoded>
					
		
		
		<post-id xmlns="com-wordpress:feed-additions:1">270907</post-id>	</item>
		<item>
		<title>Europe&#8217;s Carbon Towers Put Two Flux Correction Methods to the Test</title>
		<link>https://scienmag.com/europes-carbon-towers-put-two-flux-correction-methods-to-the-test/</link>
		
		<dc:creator><![CDATA[Russell Cooper]]></dc:creator>
		<pubDate>Fri, 09 Oct 2026 19:39:55 +0000</pubDate>
				<category><![CDATA[Athmospheric]]></category>
		<category><![CDATA[Technology and Engineering]]></category>
		<category><![CDATA[Atmospheric Measurement Techniques]]></category>
		<category><![CDATA[atmospheric measurement techniques for carbon fluxes]]></category>
		<category><![CDATA[carbon dioxide flux]]></category>
		<category><![CDATA[co-spectral correction]]></category>
		<category><![CDATA[comparison of flux correction philosophies]]></category>
		<category><![CDATA[ecosystem monitoring]]></category>
		<category><![CDATA[eddy covariance]]></category>
		<category><![CDATA[eddy-covariance stations for greenhouse gas monitoring]]></category>
		<category><![CDATA[European carbon flux measurement towers]]></category>
		<category><![CDATA[gas analyser]]></category>
		<category><![CDATA[high-frequency attenuation]]></category>
		<category><![CDATA[high-frequency attenuation correction methods]]></category>
		<category><![CDATA[ICOS]]></category>
		<category><![CDATA[ICOS network and European ecosystem monitoring]]></category>
		<category><![CDATA[implications for climate modeling and carbon budgets]]></category>
		<category><![CDATA[integration of ground-based and satellite carbon data]]></category>
		<category><![CDATA[long-term ecosystem carbon data accuracy]]></category>
		<category><![CDATA[micrometeorology]]></category>
		<category><![CDATA[multi-site studies of carbon flux correction accuracy]]></category>
		<category><![CDATA[physical limitations of eddy covariance instruments]]></category>
		<category><![CDATA[sensor separation]]></category>
		<category><![CDATA[spectral correction]]></category>
		<category><![CDATA[turbulence measurement in forests and grasslands]]></category>
		<category><![CDATA[water vapour flux]]></category>
		<guid isPermaLink="false">https://scienmag.com/?p=255617</guid>

					<description><![CDATA[A comparison across 38 ICOS stations shows that co-spectral corrections of eddy-covariance fluxes are more robust than spectral ones, especially for water vapour, and reveals systematic differences with the network's official processing pipeline.]]></description>
										<content:encoded><![CDATA[<p>Across Europe, hundreds of tall towers rise above forests, peatlands, croplands and grasslands, quietly sniffing the air twenty times per second. These eddy-covariance stations are the backbone of global carbon monitoring, providing the ground truth against which satellites and climate models are judged. But the numbers they produce are never raw: before a single flux of carbon dioxide or water vapour can be trusted, the signal must be corrected for a subtle but persistent problem known as high-frequency attenuation. A new multi-site study, published in Atmospheric Measurement Techniques, has now put the two rival correction philosophies head to head across 38 stations of the Integrated Carbon Observation System (ICOS), and the verdict carries real consequences for the reliability of long-term ecosystem data.</p>
<p>The problem the researchers tackled is fundamentally physical. Eddy-covariance instruments measure the covariance between vertical wind speed and gas concentration at high frequency, typically 10 to 20 hertz, to capture the turbulent eddies that carry gases between the surface and the atmosphere. Yet no instrument is perfect. Limited sampling time, line averaging, the physical separation between the sonic anemometer and the gas analyser&#8217;s inlet, and the passage of air through tubes and filters all act like a low-pass filter, smoothing out the fastest fluctuations. Because small eddies contribute disproportionately to the total flux, this smoothing causes a systematic underestimation that can range from a few percent to tens of percent depending on the setup, the site and the weather. Correcting for it is one of the most stubborn technical challenges in micrometeorology.</p>
<p>Two experimental strategies dominate the field. The spectral approach computes the ratio of the attenuated gas concentration power spectrum to the unattenuated sonic temperature spectrum, deriving an empirical transfer function from which a correction factor follows. The co-spectral approach instead uses the co-spectrum of the gas flux itself relative to the sensible heat flux, folding every attenuation source, including sensor separation, into a single empirical characterisation. Each camp has its defenders: spectral methods, championed by widely used software such as EddyPro and embedded in the official ICOS processing pipeline, avoid the complications of time-lag and phase-shift estimation, while co-spectral methods are immune to high-frequency noise and need no separate sensor-separation term. Until now, no systematic, network-wide comparison of the two had ever been attempted.</p>
<p>Ariane Faurès of the University of Liege and her colleagues filled that gap using a full year of carbon dioxide and water vapour flux data from 38 ICOS Class 1 and 2 ecosystem stations, all equipped with an identical enclosed-path LI-7200 gas analyser and a Gill sonic anemometer. This standardisation was a scientific gift: because every site shares the same hardware, the same heated 0.73-metre sampling line, the same rain cap and inlet filter, and flow rates fixed between 10 and 16 litres per minute, differences between sites could be attributed to atmospheric conditions and ecosystem type rather than instrument quirks. The team classified stations into high-measurement-height sites, essentially forests, and low-measurement-height sites such as croplands, grasslands and non-forested peatlands, then computed cut-off frequencies and correction factors for both methods under carefully controlled wind speed, stability and humidity classes.</p>
<p>The first headline finding is reassuring: the standardised ICOS setup performs remarkably well. Cut-off frequencies for carbon dioxide generally exceeded 1 hertz and were strikingly consistent across the continent, with a mean of 2.1 hertz and a tight spread at a wind speed of 3 metres per second. Correction factors for carbon dioxide typically stayed below 1.2, meaning the fluxes needed boosting by less than 20 percent, and often by less than 10. For water vapour the picture was harsher: attenuation was stronger, with correction factors occasionally approaching 2 under humid, windy conditions, reflecting the well-known tendency of water molecules to adsorb onto and desorb from the surfaces of the sampling tube and filter in a manner that varies with relative humidity.</p>
<p>When the two correction methods were compared directly, the differences for carbon dioxide proved small. After the standard turbulence filtering that removes weakly turbulent periods, cumulative annual flux differences between the methods typically stayed below 2 percent, and at high forest towers they were often negligible. The dominant source of carbon dioxide attenuation turned out to be sensor separation, the spatial offset between the anemometer and the analyser inlet, which the spectral approach must add back through a theoretical formulation from Horst and Lenschow. Water vapour told a different story. Here the two methods diverged substantially, with cumulative flux discrepancies frequently reaching 5 to 10 percent, and the largest gaps occurring under stable atmospheric stratification, at low measurement heights, and under strong attenuation.</p>
<p>The reasons for this divergence are methodological as much as physical. Both approaches rest on the assumption of spectral similarity, the idea that gas and temperature fluctuations share the same spectral shape at low frequencies. The study found that this assumption holds well for carbon dioxide but breaks down for water vapour, particularly in humid air, where the gas spectra departed from the ideal reference far more strongly than the co-spectra did. On top of that, the spectral approach was repeatedly plagued by high-frequency noise, requiring a dedicated denoising procedure at 58 percent of sites for carbon dioxide and 84 percent for water vapour, while the theoretical sensor-separation term it depends on produced unrealistically large corrections under stable conditions. The co-spectral approach, by contrast, delivered stable, physically consistent results across all sites and conditions, leading the authors to recommend it for this specific experimental configuration.</p>
<p>Perhaps the most provocative result emerged when the team compared their independently computed corrections with the official fluxes produced by the ICOS Ecosystem Thematic Centre. Since the network pipeline also uses a spectral method, one might expect close agreement, but the opposite was true: differences between the study&#8217;s spectral corrections and the official products were often larger than the differences between the spectral and co-spectral approaches themselves. For water vapour, cumulative flux differences against the ICOS pipeline averaged 10.7 percent at low-measurement-height sites, with some stations showing gaps exceeding 20 percent, and even carbon dioxide showed average differences of 1.6 percent and station-level extremes above 10 percent. The causes are a cascade of small choices: different low-pass and anemometer correction equations, a different sensor-separation formulation, different filtering thresholds and fitting ranges, and a contested use of the transfer function when computing correction factors, a choice that earlier work suggests can bias fluxes by up to 10 percent.</p>
<p>These numbers matter far beyond the technical community. Eddy-covariance fluxes feed the global carbon budgets that inform climate policy, underpin assessments of whether forests and peatlands are net sinks or sources of greenhouse gases, and enter the long-running debate over the surface energy balance closure problem. A systematic 10 percent uncertainty in water vapour fluxes propagates directly into estimates of evapotranspiration and ecosystem water use, while even a few percent in carbon dioxide can shift the calculated carbon balance of a young forest or a drained peatland. The study also carries a practical design lesson: because attenuation grows as the measurement height approaches the canopy, mounting sensors as high as feasible, within footprint constraints, dramatically reduces the correction burden, and at many forest towers the carbon dioxide correction is now so small it could arguably be skipped altogether.</p>
<p>The authors have released their analysis as an open-source Python tool, FreqCor, designed to be configurable across setups and trace gases, and they argue that the high-frequency correction step deserves a broader reassessment within the ICOS processing pipeline. They are candid that a fully automated, network-scale procedure remains elusive: thresholds, fitting ranges and denoising decisions still involve user judgement, and future work should replace uniform flux thresholds with signal-to-noise criteria and validate denoising across many sites. The study&#8217;s scope is limited to enclosed-path analysers, and the authors note that closed-path systems with long tubes, common for methane and nitrous oxide measurements, could show even larger method differences and merit a similar network-wide test. For now, one thing is clear: the quiet correction applied inside every flux tower&#8217;s software is not a formality, and choosing the right way to do it can change what Europe&#8217;s ecosystems appear to breathe.</p>
<p><strong>Subject of Research:</strong> Comparison of spectral and co-spectral high-frequency attenuation corrections for eddy-covariance flux measurements across the ICOS ecosystem network</p>
<p><strong>Article Title:</strong> Spectral versus co-spectral correction of eddy-covariance fluxes: a multi-site assessment across the ICOS network</p>
<p><strong>Article References:</strong> Faurès, A., Fratini, G., Nicolini, G., Papale, D., Sabbatini, S., &amp; Heinesch, B. (2026). Spectral versus co-spectral correction of eddy-covariance fluxes: a multi-site assessment across the ICOS network. <em>Atmospheric Measurement Techniques, 19</em>(18), 6037-6074. <a href="https://doi.org/10.5194/amt-19-6037-2026" rel="noopener noreferrer">https://doi.org/10.5194/amt-19-6037-2026</a></p>
<p><strong>Image Credits:</strong> AI Generated</p>
<p><strong>DOI:</strong> <a href="https://doi.org/10.5194/amt-19-6037-2026" rel="noopener noreferrer">10.5194/amt-19-6037-2026</a></p>
<p><strong>Keywords:</strong> eddy covariance, ICOS, spectral correction, co-spectral correction, high-frequency attenuation, carbon dioxide flux, water vapour flux, gas analyser, sensor separation, micrometeorology, ecosystem monitoring, Atmospheric Measurement Techniques</p>
]]></content:encoded>
					
		
		
		<post-id xmlns="com-wordpress:feed-additions:1">255617</post-id>	</item>
		<item>
		<title>Engineered T Cell Receptors With Built-In ICOS Deliver Long-Lasting Anti-Tumor Power</title>
		<link>https://scienmag.com/engineered-t-cell-receptors-with-built-in-icos-deliver-long-lasting-anti-tumor-power/</link>
		
		<dc:creator><![CDATA[Nathaniel Bowman]]></dc:creator>
		<pubDate>Sun, 13 Sep 2026 02:27:00 +0000</pubDate>
				<category><![CDATA[Cancer]]></category>
		<category><![CDATA[adoptive T cell therapy]]></category>
		<category><![CDATA[co-stimulation]]></category>
		<category><![CDATA[co-stimulatory signaling domains]]></category>
		<category><![CDATA[durable anti-tumor response]]></category>
		<category><![CDATA[Engineered T cell receptors]]></category>
		<category><![CDATA[gene engineering]]></category>
		<category><![CDATA[ICOS]]></category>
		<category><![CDATA[ICOS co-stimulator]]></category>
		<category><![CDATA[immunotherapy design]]></category>
		<category><![CDATA[melanoma]]></category>
		<category><![CDATA[melanoma mouse model]]></category>
		<category><![CDATA[Molecular Cancer]]></category>
		<category><![CDATA[NF-kappa B]]></category>
		<category><![CDATA[PI3K signaling]]></category>
		<category><![CDATA[solid tumor immunotherapy]]></category>
		<category><![CDATA[solid tumors]]></category>
		<category><![CDATA[stem-like T cells]]></category>
		<category><![CDATA[T cell exhaustion]]></category>
		<category><![CDATA[T cell longevity]]></category>
		<category><![CDATA[T cell receptor]]></category>
		<category><![CDATA[T cell receptor engineering]]></category>
		<category><![CDATA[tumor relapse prevention]]></category>
		<guid isPermaLink="false">https://scienmag.com/?p=200832</guid>

					<description><![CDATA[Researchers have engineered T cell receptors fused to the co-stimulatory molecule ICOS, producing T cells that persist longer, resist exhaustion and deliver durable anti-tumor responses in preclinical melanoma models.]]></description>
										<content:encoded><![CDATA[<p>Adoptive T cell therapy has delivered striking remissions in some blood cancers, but its promise in solid tumors has been repeatedly undermined by a stubborn problem: the therapeutic cells do not last. Engineered T cells that flood a tumor and then fade away, or that settle into a dysfunctional, exhausted state, leave the door open for relapse. A team of researchers at Erasmus MC Cancer Institute in Rotterdam, working with colleagues at Pan Cancer T BV and the Department of Immunology at Erasmus MC, now reports a design solution that attacks the longevity problem at its source. In a study published in Molecular Cancer, the group describes a rebuilt T cell receptor that carries its own co-stimulatory machinery, and shows that the resulting cells mount exceptionally durable anti-tumor responses in a mouse melanoma model, including delayed tumor recurrence and outright cures.</p>
<p>The core idea is deceptively simple. Natural T cells do not rely on their antigen receptor alone; they depend on co-stimulatory receptors such as CD28 and ICOS, the inducible T cell co-stimulator, to fine-tune activation, survival and differentiation. The researchers reasoned that if a therapeutic T cell receptor could be fused directly to a co-stimulatory signaling domain, every encounter with a tumor cell would deliver not just a recognition signal but a survival and persistence signal at the same time. The construct they engineered, which they call TCR:ICOS, combines the extracellular variable and constant domains of a conventional T cell receptor with a CD28 transmembrane segment and intracellular domains drawn from both ICOS and CD3 epsilon. The result is a single hybrid receptor that couples antigen specificity to co-stimulation in one molecular unit.</p>
<p>The functional consequences in mice were dramatic. T cells carrying the TCR:ICOS receptor showed enhanced, antigen-specific production of inflammatory cytokines, the chemical weapons that help recruit and coordinate an immune attack. More importantly, the cells persisted far longer within tumors than their conventional counterparts, and this persistence translated into clinical outcomes: delayed recurrence of melanoma and, in a subset of animals, complete and durable cures. For a field in which the transience of engineered T cells is a central bottleneck, the demonstration that a receptor-level modification can extend the working lifespan of the cells inside a hostile tumor microenvironment is a significant proof of concept.</p>
<p>Beneath the phenotypic changes lies a defined signaling logic. The team found that TCR:ICOS activation engaged two major pathways, PI3K and NF-kappa B, while paradoxically restraining the activation of AKT, a kinase downstream of PI3K that is often associated with terminal differentiation and metabolic burnout in T cells. This combination appears to be the key to the durability. Sustained PI3K and NF-kappa B signaling supports inflammatory function and survival, while blunted AKT activity helps the cells avoid the hyperactive, exhausted state that typically shortens the life of tumor-infiltrating lymphocytes. When the researchers genetically ablated the ICOS-PI3K pathway, the long-term anti-tumor effects disappeared, confirming that this signaling axis is not a side effect but the mechanistic engine of the durable response.</p>
<p>Single-cell level analysis reinforced the picture of a fundamentally altered differentiation program. TCR:ICOS T cells were enriched for a stem-like state, a less differentiated, self-renewing condition that immunologists regard as the hallmark of long-lived, re-challenge-capable T cell populations. They also showed resistance to exhaustion, the progressive loss of function marked by inhibitory receptors such as PD1, LAG3 and TIM3 that plagues conventional tumor-infiltrating cells. In practical terms, the engineered cells behaved less like short-lived commandos and more like a renewable garrison, capable of maintaining pressure on the tumor over time rather than expending themselves in a single burst of activity.</p>
<p>Translating the concept from mouse to human T cells required an additional round of molecular engineering. Early versions of the hybrid receptor did not express efficiently on the surface of human cells, a common obstacle in receptor design where folding, assembly and trafficking can fail silently. The team solved this by identifying a single amino acid change in the cytosolic tail of the receptor that enabled functional surface expression. Crucially, the optimized receptor avoided two well-known hazards of introducing engineered T cell receptors into patient cells: mispairing with endogenous TCR chains, which can create unpredictable and potentially dangerous specificities, and competition for limited CD3 molecules, which can impair the function of the T cell&#8217;s native receptor complex.</p>
<p>The human-cell experiments went beyond a single antigen. The researchers showed that the optimized TCR:ICOS format sustained the functional performance of human T cells across repeated stimulation cycles and could be extended to multiple tumor antigens, including targets relevant to solid cancers such as NY-ESO-1 and ROPN1, without eroding T cell fitness. This uniform applicability matters for the field. Many receptor-engineering advances are idiosyncratic, working for one TCR or one antigen but failing when generalized. A format that preserves T cell quality across different specificities offers a modular platform: any tumor-reactive TCR could, in principle, be equipped with the same built-in co-stimulation and inherit the same durability advantages.</p>
<p>The findings arrive at a moment when the cell therapy field is intensely focused on next-generation designs. Chimeric antigen receptors, or CARs, already incorporate co-stimulatory domains such as CD28 or 4-1BB, and that choice profoundly shapes how CAR T cells persist and differentiate. TCR-based therapies, which can recognize intracellular tumor antigens presented by HLA molecules and therefore access a much larger pool of cancer targets, have lacked an equivalent, systematic way to embed co-stimulation. The TCR:ICOS design fills that gap, and its mechanism, favoring stem-like persistence through PI3K and NF-kappa B while restraining AKT, offers a template that other groups can rationally modify.</p>
<p>There are, of course, steps between a mouse melanoma model and approved therapy. The study was conducted in preclinical systems, and human trials will need to establish safety, particularly given that engineered co-stimulation could, in principle, amplify off-tumor reactivity if a TCR recognizes healthy tissue. Dosing, manufacturing consistency and the behavior of TCR:ICOS cells in the complex, immunosuppressive environment of human solid tumors all remain to be tested. The authors note that the work was supported by the Dutch Cancer Society and a Health Holland public-private partnership, and several team members report pending patents related to the receptor design, signaling commercial interest in bringing the platform toward clinical evaluation.</p>
<p>Even so, the study offers a compelling answer to one of adoptive cell therapy&#8217;s most persistent questions: how to make engineered T cells last. By fusing recognition and co-stimulation into a single receptor, the Rotterdam team has shown that durability can be designed into the therapeutic product itself rather than bolted on with cytokines, checkpoint blockade or lymphodepleting chemotherapy. If the format performs in human trials as it has in mice, TCR:ICOS could become a foundational component of fitter, longer-lived T cell products for solid tumors, turning a transient spark of immune attack into a sustained campaign against cancer.</p>
<p><strong>Subject of Research:</strong> Engineering T cell receptors with built-in ICOS co-stimulation to extend the durability of adoptive T cell therapy against solid tumors</p>
<p><strong>Article Title:</strong> T cell receptors equipped with ICOS provide T cells with durable anti-tumor response</p>
<p><strong>Article References:</strong> Marraffa, A., Berrevoets, C., Mosiello, M., Coelho, R. M., Roelofs, D., van Brakel, M., Wijers, R., Kroese, K., Peeters, M. J., Dik, W. A., Kunert, A., Abbott, R. J., Hammerl, D., Schliehe, C., &amp; Debets, R. (2026). T cell receptors equipped with ICOS provide T cells with durable anti-tumor response. <em>Molecular Cancer, 25</em>(1), Article 216. <a href="https://doi.org/10.1186/s12943-026-02765-9" rel="noopener noreferrer">https://doi.org/10.1186/s12943-026-02765-9</a></p>
<p><strong>Image Credits:</strong> AI Generated</p>
<p><strong>DOI:</strong> <a href="https://doi.org/10.1186/s12943-026-02765-9" rel="noopener noreferrer">10.1186/s12943-026-02765-9</a></p>
<p><strong>Keywords:</strong> adoptive T cell therapy, T cell receptor, ICOS, co-stimulation, T cell exhaustion, solid tumors, melanoma, PI3K signaling, NF-kappa B, stem-like T cells, gene engineering, Molecular Cancer</p>
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