Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 47
Filtrar
1.
J Strength Cond Res ; 38(7): 1295-1299, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38900175

RESUMEN

ABSTRACT: Hill, V, Patterson, S, Buckthorpe, M, and Legg, HS. The acute effects of a preload upper-body power exercise on 50-m freestyle performance in youth swimmers. J Strength Cond Res 38(7): 1295-1299, 2024-This study aimed to investigate the acute effects of a medicine ball slam and the optimal recovery time required to induce a postactivation performance enhancement (PAPE) response on 50-meter freestyle swimming performance. Twenty-four (13 female, 11 male) competitive, adolescent swimmers (mean ± SD: age, 16.7 ± 1.2 years; height, 173.3 ± 6.7 cm; mass, 63.1 ± 6.4 kg) participated in a randomized crossover study. After the PAPE intervention (3 × 5 medicine ball slams), subjects had 1-minute, 4-minute, and 8-minute recovery periods before a 50-m maximal freestyle swim. A 1-way repeated-measures ANOVA revealed that different recovery times elicited changes in 50-m performance (F = 12.12, p < 0.0005). After 4 minutes of recovery, 50-m performance was 1.6% (0.47 seconds) faster (95% confidence interval [CI] [0.17-0.77], p < 0.001). When the data were split by sex, after 4 minutes of recovery, 50-m performance was 2% (0.64 seconds) faster for women (95% CI [0.279-0.998], p < 0.001). In conclusion, an upper-body power exercise, before performance, can induce a PAPE response and enhance 50-m freestyle performance after a 4-minute recovery period.


Asunto(s)
Rendimiento Atlético , Estudios Cruzados , Natación , Humanos , Natación/fisiología , Femenino , Adolescente , Masculino , Rendimiento Atlético/fisiología , Extremidad Superior/fisiología , Entrenamiento de Fuerza/métodos , Fuerza Muscular/fisiología
2.
Cancer Cell ; 41(12): 2154-2165.e5, 2023 12 11.
Artículo en Inglés | MEDLINE | ID: mdl-38039963

RESUMEN

Circulating T cells from peripheral blood (PBL) can provide a rich and noninvasive source for antitumor T cells. By single-cell transcriptomic profiling of 36 neoantigen-specific T cell clones from 6 metastatic cancer patients, we report the transcriptional and cell surface signatures of antitumor PBL-derived CD8+ T cells (NeoTCRPBL). Comparison of tumor-infiltrating lymphocyte (TIL)- and PBL-neoantigen-specific T cells revealed that NeoTCRPBL T cells are low in frequency and display less-dysfunctional memory phenotypes relative to their TIL counterparts. Analysis of 100 antitumor TCR clonotypes indicates that most NeoTCRPBL populations target the same neoantigens as TILs. However, NeoTCRPBL TCR repertoire is only partially shared with TIL. Prediction and testing of NeoTCRPBL signature-derived TCRs from PBL of 6 prospective patients demonstrate high enrichment of clonotypes targeting tumor mutations, a viral oncogene, and patient-derived tumor. Thus, the NeoTCRPBL signature provides an alternative source for identifying antitumor T cells from PBL of cancer patients, enabling immune monitoring and immunotherapies.


Asunto(s)
Linfocitos T CD8-positivos , Neoplasias , Humanos , Estudios Prospectivos , Antígenos de Neoplasias , Neoplasias/genética , Neoplasias/terapia , Neoplasias/metabolismo , Linfocitos Infiltrantes de Tumor , Receptores de Antígenos de Linfocitos T
3.
J Immunother Cancer ; 11(5)2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-37258038

RESUMEN

BACKGROUND: Cellular immunotherapies using autologous tumor-infiltrating lymphocytes (TIL) can induce durable regression of epithelial cancers in selected patients with treatment-refractory metastatic disease. As the genetic engineering of T cells with tumor-reactive T-cell receptors (TCRs) comes to the forefront of clinical investigation, the rapid, scalable, and cost-effective detection of patient-specific neoantigen-reactive TIL remains a top priority. METHODS: We analyzed the single-cell transcriptomic states of 31 neoantigen-specific T-cell clonotypes to identify cell surface dysfunction markers that best identified the metastatic transcriptional states enriched with antitumor TIL. We developed an efficient method to capture neoantigen-reactive TCRs directly from resected human tumors based on cell surface co-expression of CD39, programmed cell death protein-1, and TIGIT dysfunction markers (CD8+ TILTP). RESULTS: TILTP TCR isolation achieved a high degree of correlation with single-cell transcriptomic signatures that identify neoantigen-reactive TCRs, making it a cost-effective strategy using widely available resources. Reconstruction of additional TILTP TCRs from tumors identified known and novel antitumor TCRs, showing that at least 39.5% of TILTP TCRs are neoantigen-reactive or tumor-reactive. Despite their substantial enrichment for neoantigen-reactive TCR clonotypes, clonal dynamics of 24 unique antitumor TILTP clonotypes from four patients indicated that most in vitro expanded TILTP populations failed to demonstrate neoantigen reactivity, either by loss of neoantigen-reactive clones during TIL expansion, or through functional impairment during cognate neoantigen recognition. CONCLUSIONS: While direct usage of in vitro-expanded CD8+ TILTP as a source for cellular therapy might be precluded by profound TIL dysfunction, isolating TILTP represents a streamlined effective approach to rapidly identify neoantigen-reactive TCRs to design engineered cellular immunotherapies against cancer.


Asunto(s)
Antígenos de Neoplasias , Neoplasias , Humanos , Linfocitos T CD8-positivos , Neoplasias/metabolismo , Receptores de Antígenos de Linfocitos T , Linfocitos Infiltrantes de Tumor
4.
J Immunother Cancer ; 11(4)2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-37045473

RESUMEN

BACKGROUND: Metastatic cholangiocarcinoma (CC), a form of gastrointestinal cancer that originates from the bile ducts, cannot be cured by currently available therapies, and is associated with dismal prognosis. In a previous case report, adoptive transfer of autologous tumor infiltrating lymphocytes (TILs), the majority of which recognized a tumor-specific point mutation, led to a profound and durable cancer regression in a patient with metastatic CC. Thus, more effective treatment for patients with this disease may be developed by using TILs that target cancer-specific mutations, but also other genetic aberrations such as gene fusions. In this context, fusions that involve fibroblast growth factor receptor 2 (FGFR2) and function as oncogenes in a subset of patients with intrahepatic CC (ICC) represent particularly attractive targets for adoptive cell therapy. However, no study to date has explored whether FGFR2 fusions can be recognized by patients' T cells. METHOD: To address whether FGFR2 fusions can be recognized by patients' T cells, we tested TILs from four patients with FGFR2 fusion-positive ICC for recognition of peptides and minigenes that represented the breakpoint regions of these fusions, which were unique to each of the four patients. RESULTS: We found that CD4+ TILs from one patient specifically recognized the breakpoint region of a unique FGFR2-TDRD1 (tudor domain-containing 1) fusion, and we isolated a T-cell receptor responsible for its recognition. CONCLUSIONS: This finding suggests that FGFR2 fusion-reactive TILs can be isolated from some patients with metastatic ICC, and thus provides a rationale for future exploration of T cell-based therapy targeting FGFR2 fusions in patients with cancer. Furthermore, it augments the rationale for extending such efforts to other types of solid tumors hallmarked by oncogenic gene fusions.


Asunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Humanos , Neoplasias de los Conductos Biliares/genética , Neoplasias de los Conductos Biliares/patología , Conductos Biliares Intrahepáticos/metabolismo , Conductos Biliares Intrahepáticos/patología , Colangiocarcinoma/patología , Linfocitos Infiltrantes de Tumor/metabolismo , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/genética , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/metabolismo
5.
J Environ Manage ; 337: 117669, 2023 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-36966636

RESUMEN

Seagrasses have been widely recognized for their ecosystem services, but traditional seagrass monitoring approaches emphasizing ground and aerial observations are costly, time-consuming, and lack standardization across datasets. This study leveraged satellite imagery from Maxar's WorldView-2 and WorldView-3 high spatial resolution, commercial satellite platforms to provide a consistent classification approach for monitoring seagrass at eleven study areas across the continental United States, representing geographically, ecologically, and climatically diverse regions. A single satellite image was selected at each of the eleven study areas to correspond temporally to reference data representing seagrass coverage and was classified into four general classes: land, seagrass, no seagrass, and no data. Satellite-derived seagrass coverage was then compared to reference data using either balanced agreement, the Mann-Whitney U test, or the Kruskal-Wallis test, depending on the format of the reference data used for comparison. Balanced agreement ranged from 58% to 86%, with better agreement between reference- and satellite-indicated seagrass absence (specificity ranged from 88% to 100%) than between reference- and satellite-indicated seagrass presence (sensitivity ranged from 17% to 73%). Results of the Mann-Whitney U and Kruskal-Wallis tests demonstrated that satellite-indicated seagrass percentage cover had moderate to large correlations with reference-indicated seagrass percentage cover, indicative of moderate to strong agreement between datasets. Satellite classification performed best in areas of dense, continuous seagrass compared to areas of sparse, discontinuous seagrass and provided a suitable spatial representation of seagrass distribution within each study area. This study demonstrates that the same methods can be applied across scenes spanning varying seagrass bioregions, atmospheric conditions, and optical water types, which is a significant step toward developing a consistent, operational approach for mapping seagrass coverage at the national and global scales. Accompanying this manuscript are instructional videos describing the processing workflow, including data acquisition, data processing, and satellite image classification. These instructional videos may serve as a management tool to complement field- and aerial-based mapping efforts for monitoring seagrass ecosystems.


Asunto(s)
Ecosistema , Imágenes Satelitales , Estados Unidos , Monitoreo del Ambiente/métodos
6.
Remote Sens (Basel) ; 15(19): 1-25, 2023 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-38362160

RESUMEN

Mapping the seagrass distribution and density in the underwater landscape can improve global Blue Carbon estimates. However, atmospheric absorption and scattering introduce errors in space-based sensors' retrieval of sea surface reflectance, affecting seagrass presence, density, and above-ground carbon (AGCseagrass) estimates. This study assessed atmospheric correction's impact on mapping seagrass using WorldView-2 satellite imagery from Saint Joseph Bay, Saint George Sound, and Keaton Beach in Florida, USA. Coincident in situ measurements of water-leaving radiance (LW), optical properties, and seagrass leaf area index (LAI) were collected. Seagrass classification and the retrieval of LAI were compared after empirical line height (ELH) and dark-object subtraction (DOS) methods were used for atmospheric correction. DOS left residual brightness in the blue and green bands but had minimal impact on the seagrass classification accuracy. However, the brighter reflectance values reduced LAI retrievals by up to 50% compared to ELH-corrected images and ground-based observations. This study offers a potential correction for LAI underestimation due to incomplete atmospheric correction, enhancing the retrieval of seagrass density and above-ground Blue Carbon from WorldView-2 imagery without in situ observations for accurate atmospheric interference correction.

7.
Front Plant Sci ; 13: 1025416, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36438084

RESUMEN

Photorespiration, commonly viewed as a loss in photosynthetic productivity of C3 plants, is expected to decline with increasing atmospheric CO2, even though photorespiration plays an important role in the oxidative stress responses. This study aimed to quantify the role of photorespiration and alternative photoprotection mechanisms in Zostera marina L. (eelgrass), a carbon-limited marine C3 plant, in response to ocean acidification. Plants were grown in controlled outdoor aquaria at different [CO2]aq ranging from ~55 (ambient) to ~2121 µM for 13 months and compared for differences in leaf photochemistry by simultaneous measurements of O2 flux and variable fluorescence. At ambient [CO2], photosynthesis was carbon limited and the excess photon absorption was diverted both to photorespiration and non-photochemical quenching (NPQ). The dynamic range of NPQ regulation in ambient grown plants, in response to instantaneous changes in [CO2]aq, suggested considerable tolerance for fluctuating environmental conditions. However, 60 to 80% of maximum photosynthetic capacity of ambient plants was diverted to photorespiration resulting in limited carbon fixation. The photosynthesis to respiration ratio (P E : R D) of ambient grown plants increased 6-fold when measured under high CO2 because photorespiration was virtually suppressed. Plants acclimated to high CO2 maintained 4-fold higher P E : R D than ambient grown plants as a result of a 60% reduction in photorespiration. The O2 production efficiency per unit chlorophyll was not affected by the CO2 environment in which the plants were grown. Yet, CO2 enrichment decreased the light level to initiate NPQ activity and downregulated the biomass specific pigment content by 50% and area specific pigment content by 30%. Thus, phenotypic acclimation to ocean carbonation in eelgrass, indicating the coupling between the regulation of photosynthetic structure and metabolic carbon demands, involved the downregulation of light harvesting by the photosynthetic apparatus, a reduction in the role of photorespiration and an increase in the role of NPQ in photoprotection. The quasi-mechanistic model developed in this study permits integration of photosynthetic and morphological acclimation to ocean carbonation into seagrass productivity models, by adjusting the limits of the photosynthetic parameters based on substrate availability and physiological capacity.

8.
Limnol Oceanogr ; 67(6): 1374-1387, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36248249

RESUMEN

Oceanographic lidar measurements of the linear depolarization ratio, δ, contain information on the bulk characteristics of marine particles that could improve our ability to study ocean biogeochemistry. However, a scarcity of information on the polarized light-scattering properties of marine particles and the lack of a framework for separating single and multiple scattering effects on δ have hindered the development of polarization-based retrievals of bulk particle properties. To address these knowledge gaps, we made single scattering measurements of δ for several compositionally and morphologically distinct marine particle assemblages. We then used a bio-optical model to explore the influence of multiple scattering and particle characteristics on lidar measurements of δ made during an expedition to sample a mesoscale coccolithophore bloom. Laboratory measurements of linear depolarization revealed a complex dependency on particle shape, size, and composition that were consistent with scattering simulations for idealized nonspherical particles. Model results suggested that the variability in δ measured during the field expedition was driven predominantly by shifts in particle concentration rather than their bulk characteristics. However, model estimates of δ improved when calcite particles were represented by a distinct particle class, highlighting the influence of bulk particle properties on δ. To advance polarized lidar retrievals of bulk particle properties and to constrain the uncertainty in satellite lidar retrievals of particulate backscattering, these results point to the need for future efforts to characterize the variability of particulate depolarization in the ocean and to quantify the sensitivity of operational ocean lidar systems to multiple scattering.

9.
Mar Environ Res ; 179: 105694, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35850077

RESUMEN

Seagrass meadows are degraded globally and continue to decline in areal extent due to human pressures and climate change. This study used the bio-optical model GrassLight to explore the impact of climate change and anthropogenic stressors on seagrass extent, leaf area index (LAI) and belowground organic carbon (BGC) in St. Joseph Bay, Florida, using water quality data and remotely-sensed sea surface temperature (SST) from 2002 to 2020. Model predictions were compared with satellite-derived measurements of seagrass extent and shoot density from the Landsat images for the same period. The GrassLight-derived area of potential seagrass habitat ranged from 36.2 km2 to 39.2 km2, averaging 38.0 ± 0.8 km2 compared to an observed seagrass extent of 23.0 ± 3.0 km2 derived from Landsat (range = 17.9-27.4 km2). GrassLight predicted a mean seagrass LAI of 2.7 m2 leaf m-2 seabed, compared to a mean LAI of 1.9 m2 m-2 estimated from Landsat, indicating that seagrass density in St. Joseph Bay may have been below its light-limited ecological potential. Climate and anthropogenic change simulations using GrassLight predicted the impact of changes in temperature, pH, chlorophyll a, chromophoric dissolved organic matter and turbidity on seagrass meadows. Simulations predicted a 2-8% decline in seagrass extent with rising temperatures that was offset by a 3-11% expansion in seagrass extent in response to ocean acidification when compared to present conditions. Simulations of water quality impacts showed that a doubling of turbidity would reduce seagrass extent by 18% and total leaf area by 21%. Combining climate and water quality scenarios showed that ocean acidification may increase seagrass productivity to offset the negative effects of both thermal stress and declining water quality on the seagrasses growing in St. Joseph Bay. This research highlights the importance of considering multiple limiting factors in understanding the effects of environmental change on seagrass ecosystems.


Asunto(s)
Carbono , Ecosistema , Bahías , Clorofila A , Florida , Humanos , Concentración de Iones de Hidrógeno , Agua de Mar
10.
Cancer Immunol Res ; 10(8): 932-946, 2022 08 03.
Artículo en Inglés | MEDLINE | ID: mdl-35749374

RESUMEN

Adoptive cellular therapy (ACT) targeting neoantigens can achieve durable clinical responses in patients with cancer. Most neoantigens arise from patient-specific mutations, requiring highly individualized treatments. To broaden the applicability of ACT targeting neoantigens, we focused on TP53 mutations commonly shared across different cancer types. We performed whole-exome sequencing on 163 patients with metastatic solid cancers, identified 78 who had TP53 missense mutations, and through immunologic screening, identified 21 unique T-cell reactivities. Here, we report a library of 39 T-cell receptors (TCR) targeting TP53 mutations shared among 7.3% of patients with solid tumors. These TCRs recognized tumor cells in a TP53 mutation- and human leucocyte antigen (HLA)-specific manner in vitro and in vivo. Twelve patients with chemorefractory epithelial cancers were treated with ex vivo-expanded autologous tumor-infiltrating lymphocytes (TIL) that were naturally reactive against TP53 mutations. However, limited clinical responses (2 partial responses among 12 patients) were seen. These infusions contained low frequencies of mutant p53-reactive TILs that had exhausted phenotypes and showed poor persistence. We also treated one patient who had chemorefractory breast cancer with ACT comprising autologous peripheral blood lymphocytes transduced with an allogeneic HLA-A*02-restricted TCR specific for p53R175H. The infused cells exhibited an improved immunophenotype and prolonged persistence compared with TIL ACT and the patient experienced an objective tumor regression (-55%) that lasted 6 months. Collectively, these proof-of-concept data suggest that the library of TCRs targeting shared p53 neoantigens should be further evaluated for the treatment of patients with advanced human cancers. See related Spotlight by Klebanoff, p. 919.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Neoplasias , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/inmunología , Genes Codificadores de los Receptores de Linfocitos T , Humanos , Linfocitos Infiltrantes de Tumor/inmunología , Neoplasias/genética , Neoplasias/terapia , Receptores de Antígenos de Linfocitos T/inmunología , Linfocitos T/inmunología , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/inmunología
11.
Int J Remote Sens ; 43(4): 1199-1225, 2022 Mar 02.
Artículo en Inglés | MEDLINE | ID: mdl-35769209

RESUMEN

Satellite image artefacts are features that appear in an image but not in the original imaged object and can negatively impact the interpretation of satellite data. Vertical artefacts are linear features oriented in the along-track direction of an image system and can present as either banding or striping; banding are features with a consistent width, and striping are features with inconsistent widths. This study used high-resolution data from DigitalGlobe's (now Maxar) WorldView-3 satellite collected at Lake Okeechobee, Florida (FL), on 30 August 2017. This study investigated the impact of vertical artefacts on both at-sensor radiance and a spectral index for an aquatic target as WorldView-3 was primarily designed as a land sensor. At-sensor radiance measured by six of WorldView-3's eight spectral bands exhibited banding, more specifically referred to as non-uniformity, at a width corresponding to the multispectral detector sub-arrays that comprise the WorldView-3 focal plane. At-sensor radiance measured by the remaining two spectral bands, red and near-infrared (NIR) #1, exhibited striping. Striping in these spectral bands can be attributed to their time delay integration (TDI) settings at the time of image acquisition, which were optimized for land. The impact of vertical striping on a spectral index leveraging the red, red edge, and NIR spectral bands-referred to here as the NIR maximum chlorophyll index (MCINIR)-was investigated. Temporally similar imagery from the European Space Agency's Sentinel-3 and Sentinel-2 satellites were used as baseline references of expected chlorophyll values across Lake Okeechobee as neither Sentinel-3 nor Sentinel-2 imagery showed striping. Striping was highly prominent in the MCINIR product generated using WorldView-3 imagery, as noise in the at-sensor radiance exceeded any signal of chlorophyll in the image. Adjusting the image acquisition parameters for future tasking of WorldView-3 or the functionally similar WorldView-2 satellite may alleviate these artefacts. To test this, an additional WorldView-3 image was acquired at Lake Okeechobee, FL, on 26 May 2021 in which the TDI settings and scan line rate were adjusted to improve the signal-to-noise ratio. While some evidence of non-uniformity remained, striping was no longer noticeable in the MCINIR product. Future image tasking over aquatic targets should employ these updated image acquisition parameters. Since the red and NIR #1 spectral bands are critical for inland and coastal water applications, archived images not collected using these updated settings may be limited in their potential for analysis of aquatic variables that require these two spectral bands to derive.

12.
Science ; 375(6583): 877-884, 2022 02 25.
Artículo en Inglés | MEDLINE | ID: mdl-35113651

RESUMEN

The accurate identification of antitumor T cell receptors (TCRs) represents a major challenge for the engineering of cell-based cancer immunotherapies. By mapping 55 neoantigen-specific TCR clonotypes (NeoTCRs) from 10 metastatic human tumors to their single-cell transcriptomes, we identified signatures of CD8+ and CD4+ neoantigen-reactive tumor-infiltrating lymphocytes (TILs). Neoantigen-specific TILs exhibited tumor-specific expansion with dysfunctional phenotypes, distinct from blood-emigrant bystanders and regulatory TILs. Prospective prediction and testing of 73 NeoTCR signature-derived clonotypes demonstrated that half of the tested TCRs recognized tumor antigens or autologous tumors. NeoTCR signatures identified TCRs that target driver neoantigens and nonmutated viral or tumor-associated antigens, suggesting a common metastatic TIL exhaustion program. NeoTCR signatures delineate the landscape of TILs across metastatic tumors, enabling successful TCR prediction based purely on TIL transcriptomic states for use in cancer immunotherapy.


Asunto(s)
Antígenos de Neoplasias/inmunología , Linfocitos Infiltrantes de Tumor/inmunología , Metástasis de la Neoplasia , Neoplasias/inmunología , Receptores de Antígenos de Linfocitos T/inmunología , Linfocitos T/inmunología , Transcriptoma , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Redes Reguladoras de Genes , Humanos , Linfocitos Infiltrantes de Tumor/metabolismo , Neoplasias/genética , Neoplasias/metabolismo , RNA-Seq , Análisis de la Célula Individual
13.
J Clin Oncol ; 40(16): 1741-1754, 2022 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-35104158

RESUMEN

PURPOSE: Metastatic breast cancer (mBrCa) is most often an incurable disease with only modest responses to available immunotherapies. This study investigates the immunogenicity of somatic mutations in breast cancer and explores the therapeutic efficacy in a pilot trial of mutation-reactive tumor-infiltrating lymphocytes (TILs) in patients with metastatic disease. PATIENTS AND METHODS: Forty-two patients with mBrCa refractory to previous lines of treatment underwent surgical resection of a metastatic lesion(s), isolation of TIL cultures, identification of exomic nonsynonymous tumor mutations, and immunologic screening for neoantigen reactivity. Clinically eligible patients with appropriate reactivity were enrolled into one cohort of an ongoing phase II pilot trial of adoptive cell transfer of selected neoantigen-reactive TIL, with a short course of pembrolizumab (ClinicalTrials.gov identifier: NCT01174121). RESULTS: TILs were isolated and grown in culture from the resected lesions of all 42 patients with mBrCa, and a median number of 112 (range: 6-563) nonsynonymous mutations per patient were identified. Twenty-eight of 42 (67%) patients contained TIL that recognized at least one immunogenic somatic mutation (median: 3 neoantigens per patient, range: 1-11), and 13 patients demonstrated robust reactivity appropriate for adoptive transfer. Eight patients remained clinically eligible for treatment, and six patients were enrolled on a protocol of adoptive cell transfer of enriched neoantigen-specific TIL, in combination with pembrolizumab (≤ 4 doses). Objective tumor regression was noted in three patients, including one complete response (now ongoing over 5.5 years) and two partial responses (6 and 10 months). CONCLUSION: Most patients with breast cancer generated a natural immune response targeting the expressed products of their cancer mutations. Adoptive transfer of TIL is a highly personalized experimental option for patients with mBrCa shown to be capable of mediating objective responses in this pilot trial and deserves further study.


Asunto(s)
Neoplasias de la Mama , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Femenino , Humanos , Inmunoterapia Adoptiva/métodos , Linfocitos Infiltrantes de Tumor , Mutación , Trasplante Autólogo
14.
Estuaries Coast ; 45: 2082-2101, 2022 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37009415

RESUMEN

Seagrasses are globally recognized for their contribution to blue carbon sequestration. However, accurate quantification of their carbon storage capacity remains uncertain due, in part, to an incomplete inventory of global seagrass extent and assessment of its temporal variability. Furthermore, seagrasses are undergoing significant decline globally, which highlights the urgent need to develop change detection techniques applicable to both the scale of loss and the spatial complexity of coastal environments. This study applied a deep learning algorithmto a 30-year time series of Landsat 5 through 8 imagery to quantify seagrass extent, leaf area index (LAI), and belowground organic carbon (BGC) in St. Joseph Bay, Florida, between 1990 and 2020. Consistent with previous field-based observations regarding stability of seagrass extent throughout St. Joseph Bay, there was no temporal trend in seagrass extent (23 ± 3 km2, τ = 0.09, p = 0.59, n = 31), LAI (1.6 ± 0.2, τ = -0.13, p = 0.42, n = 31), or BGC (165 ± 19 g C m-2, τ = - 0.01, p = 0.1, n = 31) over the 30-year study period. There were, however, six brief declines in seagrass extent between the years 2004 and 2019 following tropical cyclones, from which seagrasses recovered rapidly. Fine-scale interannual variability in seagrass extent, LAI, and BGC was unrelated to sea surface temperature or to climate variability associated with the El Niño-Southern Oscillation or the North Atlantic Oscillation. Although our temporal assessment showed that seagrass and its belowground carbon were stable in St. Joseph Bay from 1990 to 2020, forecasts suggest that environmental and climate pressures are ongoing, which highlights the importance of the method and time series presented here as a valuable tool to quantify decadal-scale variability in seagrass dynamics. Perhaps more importantly, our results can serve as a baseline against which we can monitor future change in seagrass communities and their blue carbon.

15.
J Immunother Cancer ; 9(7)2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34266885

RESUMEN

The adoptive transfer of naturally occurring T cells that recognize cancer neoantigens has led to durable tumor regressions in select patients with cancer. However, it remains unknown whether such T cells can be isolated from and used to treat patients with glioblastoma, a cancer that is refractory to currently available therapies. To answer this question, we stimulated patient blood-derived memory T cells in vitro using peptides and minigenes that represented point mutations unique to patients' tumors (ie, candidate neoantigens) and then tested their ability to specifically recognize these mutations. In a cohort of five patients with glioblastoma, we found that circulating CD4+ memory T cells from one patient recognized a cancer neoantigen harboring a mutation in the EED gene (EEDH189N) that was unique to that patient's tumor. This finding suggests that neoantigen-reactive T cells could indeed be isolated from patients with glioblastoma, thereby providing a rationale for further efforts to develop neoantigen-directed adoptive T cell therapy for this disease.


Asunto(s)
Glioblastoma/inmunología , Linfocitos Infiltrantes de Tumor/inmunología , Humanos
16.
Science ; 370(6522): 1328-1334, 2020 12 11.
Artículo en Inglés | MEDLINE | ID: mdl-33303615

RESUMEN

Adoptive T cell therapy (ACT) using ex vivo-expanded autologous tumor-infiltrating lymphocytes (TILs) can mediate complete regression of certain human cancers. The impact of TIL phenotypes on clinical success of TIL-ACT is currently unclear. Using high-dimensional analysis of human ACT products, we identified a memory-progenitor CD39-negative stem-like phenotype (CD39-CD69-) associated with complete cancer regression and TIL persistence and a terminally differentiated CD39-positive state (CD39+CD69+) associated with poor TIL persistence. Most antitumor neoantigen-reactive TILs were found in the differentiated CD39+ state. However, ACT responders retained a pool of CD39- stem-like neoantigen-specific TILs that was lacking in ACT nonresponders. Tumor-reactive stem-like TILs were capable of self-renewal, expansion, persistence, and superior antitumor response in vivo. These data suggest that TIL subsets mediating ACT response are distinct from TIL subsets enriched for antitumor reactivity.


Asunto(s)
Linfocitos T CD8-positivos/inmunología , Inmunoterapia Adoptiva/métodos , Linfocitos Infiltrantes de Tumor/trasplante , Melanoma/terapia , Neoplasias Cutáneas/terapia , Animales , Antígenos CD/análisis , Antígenos de Diferenciación de Linfocitos T/análisis , Apirasa/análisis , Linfocitos T CD8-positivos/química , Femenino , Humanos , Lectinas Tipo C/análisis , Melanoma/inmunología , Ratones , Ratones Mutantes , Neoplasias Cutáneas/inmunología
17.
Data Sci Eng ; 5(2): 111-125, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32685664

RESUMEN

Seagrass form the basis for critically important marine ecosystems. Previously, we implemented a deep convolutional neural network (CNN) model to detect seagrass in multispectral satellite images of three coastal habitats in northern Florida. However, a deep CNN model trained at one location usually does not generalize to other locations due to data distribution shifts. In this paper, we developed a semi-supervised domain adaptation method to generalize a trained deep CNN model to other locations for seagrass detection. First, we utilized a generative adversarial network loss to align marginal data distribution between source domain and target domain using unlabeled data from both data domains. Second, we used a few labelled samples from the target domain to align class specific data distributions between the two domains, based on the contrastive semantic alignment loss. We achieved the best results in 28 out of 36 scenarios as compared to other state-of-the-art domain adaptation methods.

18.
Appl Opt ; 59(15): 4650-4662, 2020 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-32543574

RESUMEN

Oceanographic lidar can provide remote estimates of the vertical distribution of suspended particles in natural waters, potentially revolutionizing our ability to characterize marine ecosystems and properly represent them in models of upper ocean biogeochemistry. However, lidar signals exhibit complex dependencies on water column inherent optical properties (IOPs) and instrument characteristics, which complicate efforts to derive meaningful biogeochemical properties from lidar return signals. In this study, we used a ship-based system to measure the lidar attenuation coefficient (α) and linear depolarization ratio (δ) across a variety of optically and biogeochemically distinct water masses, including turbid coastal waters, clear oligotrophic waters, and calcite rich waters associated with a mesoscale coccolithophore bloom. Sea surface IOPs were measured continuously while underway to characterize the response of α and δ to changes in particle abundance and composition. The magnitude of α was consistent with the diffuse attenuation coefficient (Kd), though the α versus Kd relationship was nonlinear. δ was positively related to the scattering optical depth and the calcite fraction of backscattering. A statistical fit to these data suggests that the polarized scattering properties of calcified particles are distinct and contribute to measurable differences in the lidar depolarization ratio. A better understanding of the polarized scattering properties of coccolithophores and other marine particles will further our ability to interpret polarized oceanographic lidar measurements and may lead to new techniques for measuring the material properties of marine particles remotely.


Asunto(s)
Luz , Fitoplancton/fisiología , Dispersión de Radiación , Ecosistema , Monitoreo del Ambiente/métodos , Oceanografía , Océanos y Mares , Óptica y Fotónica , Agua/química
19.
Remote Sens Environ ; 250: 112036, 2020 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-34334824

RESUMEN

Satellite remote sensing offers an effective remedy to challenges in ground-based and aerial mapping that have previously impeded quantitative assessments of global seagrass extent. Commercial satellite platforms offer fine spatial resolution, an important consideration in patchy seagrass ecosystems. Currently, no consistent protocol exists for image processing of commercial data, limiting reproducibility and comparison across space and time. Additionally, the radiometric performance of commercial satellite sensors has not been assessed against the dark and variable targets characteristic of coastal waters. This study compared data products derived from two commercial satellites: DigitalGlobe's WorldView-2 and Planet's RapidEye. A single scene from each platform was obtained at St. Joseph Bay in Florida, USA, corresponding to a November 2010 field campaign. A reproducible processing regime was developed to transform imagery from basic products, as delivered from each company, into analysis-ready data usable for various scientific applications. Satellite-derived surface reflectances were compared against field measurements. WorldView-2 imagery exhibited high disagreement in the coastal blue and blue spectral bands, chronically overpredicting. RapidEye exhibited better agreement than WorldView-2, but overpredicted slightly across all spectral bands. A deep convolutional neural network was used to classify imagery into deep water, land, submerged sand, seagrass, and intertidal classes. Classification results were compared to seagrass maps derived from photointerpreted aerial imagery. This study offers the first radiometric assessment of WorldView-2 and RapidEye over a coastal system, revealing inherent calibration issues in shorter wavelengths of WorldView-2. Both platforms demonstrated as much as 97% agreement with aerial estimates, despite differing resolutions. Thus, calibration issues in WorldView-2 did not appear to interfere with classification accuracy, but could be problematic if estimating biomass. The image processing routine developed here offers a reproducible workflow for WorldView-2 and RapidEye imagery, which was tested in two additional coastal systems. This approach may become platform independent as more sensors become available.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...