STRAP Knockdown Inhibits Migration and Growth of Non-Small Cell Lung Cancer.

Serine-threonine kinase receptor-associated protein (STRAP) regulates cell proliferation and apoptosis by binding to many target proteins and plays an important regulatory role in tumor development. We studied the effects of STRAP on non-small cell lung cancer (NSCLC) in vivo and in vitro in order to elucidate possible mechanisms underlying the regulatory effects of this protein. The levels of STRAP in NSCLC tissues and cells were determined by quantitative reverse transcription PCR, immunohistochemical staining, and Western blotting. In in vitro experiments, A549 and HCC827 cells were transfected with small interfering RNA (siRNA) to knockdown STRAP (si-STRAP) or with negative control sequence; cell migration and invasion were detected by scratch and Transwell assays, respectively. The expression levels of X-linked inhibitor of apoptosis protein (XIAP), caspase-3, and caspase-9 were determined by Western blotting. In addition, we analyzed changes of tumor volume in a nude mouse NSCLC model. STRAP was highly expressed in NSCLC tissues and cells, but its expression was significantly suppressed in A549 and HCC827 cells transfected with si-STRAP. STRAP knockdown resulted in a significant inhibition of migration and invasion of A549 and HCC827 cells. It also significantly reduced the expression of XIAP and elevated expression of caspase-3 and caspase-9. In nude mice with tumor originated from transplanted A549 cells, inhibition of STRAP expression retarded the tumor growth. Overall, these findings indicate that STRAP is overexpressed in NSCLC, while knockdown of STRAP gene inhibits the growth of NSCLC.

Gemcitabine, carboplatin, and Epstein-Barr virus-specific autologous cytotoxic T lymphocytes for recurrent or metastatic nasopharyngeal carcinoma: VANCE, an international randomized phase III trial.

BACKGROUND: Epstein-Barr virus-specific cytotoxic T lymphocyte (EBV-CTL) is an autologous adoptive T-cell immunotherapy generated from the blood of individuals and manufactured without genetic modification. In a previous phase II trial of locally recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) patients, first-line gemcitabine and carboplatin (GC) and EBV-CTL combination demonstrated objective antitumor EBV-CTL activity and a favorable safety profile. The present study explored whether this combined first-line chemo-immunotherapy strategy would produce superior clinical efficacy and better quality of life compared with conventional chemotherapy treatment. PATIENTS AND METHODS: This multicenter, randomized, phase III trial evaluated the efficacy and safety of GC followed by EBV-CTL versus GC alone as first-line treatment of R/M NPC patients. Thirty clinical sites in Singapore, Malaysia, Taiwan, Thailand, and the USA were included. Subjects were randomized to first-line GC (four cycles) and EBV-CTL (six cycles) or GC (six cycles) in a 1 : 1 ratio. The primary outcome was overall survival (OS) and secondary outcomes included progression-free survival, objective response rate, clinical benefit rate, quality of life, and safety. CLINICALTRIALS: gov identifier: NCT02578641. RESULTS: A total of 330 subjects with NPC were enrolled. Most subjects in both treatment arms received four or more cycles of chemotherapy and most subjects in the GC + EBV-CTL group received two or more infusions of EBV-CTL. The central Good Manufacturing Practices (GMP) facility produced sufficient EBV-CTL for 94% of GC + EBV-CTL subjects. The median OS was 25.0 months in the GC + EBV-CTL group and 24.9 months in the GC group (hazard ratio = 1.19; 95% confidence interval 0.91-1.56; P = 0.194). Only one subject experienced a grade 2 serious adverse event related to EBV-CTL. CONCLUSIONS: GC + EBV-CTL in subjects with R/M NPC demonstrated a favorable safety profile but no overall improvement in OS versus chemotherapy. This is the largest adoptive T-cell therapy trial reported in solid tumors to date.

A Q-band frequency tunable Doppler backscattering (DBS) system for pedestal and scrape-off layer density fluctuation and flow measurements in the DIII-D tokamak.

We present the design and laboratory tests for a new Q-band frequency tunable Doppler backscattering (DBS) system suitable for probing poloidal wavenumber kñ = 6-8 cm-1 density fluctuations and their flow velocities in the pedestal and scape-off layer (SOL) of the DIII-D tokamak. This system will provide new measurements in the increasingly important and under-diagnosed far pedestal and SOL plasma regions. These results are important for experimental transport studies and necessary for the validation of transport models, both of which are important to fusion energy research. The use of a single tunable frequency reduces the complexity and potential failure points as compared to a multichannel system. This new system utilizes a 33-50 GHz tunable source and will be integrated into the current V-band DBS in DIII-D using a broadband Q- and V-band multiplexer. A full-scale mockup of the quasi-optical system was used to test and optimize the performance. These tests include beam profile measurements at different distances (and angles) from a paraboloidal focusing and steering mirror. The measurements cover the full frequency range 33-75 GHz of the integrated/combined Q-V band DBS system and target a large radial coverage of the low-field side of the plasma from ρ = 1.1 to ρ = 0.5, where ρ is the normalized flux surface radial coordinate.

New millimeter-wave diagnostics to locally probe internal density and magnetic field fluctuations in National Spherical Torus Experiment-Upgrade (invited).

A set of new millimeter-wave diagnostics will deliver unique measurement capabilities for National Spherical Torus Experiment-Upgrade to address a variety of plasma instabilities believed to be important in determining thermal and particle transport, such as micro-tearing, global Alfvén eigenmodes, kinetic ballooning, trapped electron, and electron temperature gradient modes. These diagnostics include a new integrated intermediate-k Doppler backscattering (DBS) and cross-polarization scattering (CPS) system (four channels, 82.5-87 GHz) to measure density and magnetic fluctuations, respectively. The system can access reasonably large normalized wavenumbers kθρs ranging from ≤0.5 to 15 (where ion sound gyroradius ρs = 1 cm and kθ is the binormal density turbulence wavenumber). The system addresses the challenges for making useful DBS/CPS measurements with a remote control of launch polarization (X- or O-mode), probed wavenumber, polarization match of the launch beam with the edge magnetic field pitch angle, and beam steering of the launched beam for wave-vector alignment. In addition, a low-k DBS system consisting of eight fixed frequencies (34-52 GHz) and four tunable frequencies (55-75 GHz) for low-k density turbulence and fast ion physics will be located at a nearby port location. The combined systems cover the near LCFS and pedestal regions (34-52 GHz), the pedestal or mid-radius (50-75 GHz), and core plasmas (82.5-87 GHz).

[Clinicopathological features and prognosis of sporadic mismatch repair deficient colorectal cancer].

Objective: To investigate the clinicopathological characteristics and prognostic factors of sporadic mismatch repair deficient (dMMR) colorectal cancer. Methods: A total of 120 cases of sporadic dMMR colorectal cancer from July 2015 to April 2021 were retrospectively collected in Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Patients with Lynch syndrome; synchronous multiple colorectal cancers; preoperative anti-tumor treatments such as chemotherapy and radiotherapy; and those with incomplete follow-up information were excluded based on family history and next-generation sequencing (NGS) test results. Immunohistochemical stains were used to detect the expression of mismatch repair proteins, methylation-specific PCR for methylation testing, and fluorescent PCR for BRAF V600E gene mutation detection. The clinical and pathological data, and gene mutation status were analyzed. Follow-up was done to assess survival and prognosis including progression-free survival and overall survival rate. Results: Sporadic dMMR colorectal cancer occurred more frequently in the right side of the colon, in females, and in the elderly. Morphologically, it was mostly moderately-differentiated, and most patients had low-grade tumor budding. In terms of immunohistochemical expression, MLH1 and PMS2 loss were dominant, and there were age and location-specificities in protein expression. MLH1 methylation was commonly detected in elderly female patients and rare in young male patients; while MLH1 and PMS2 deficiency, and BRAF V600E mutation occurred more often on the right side (P<0.05). The 3-year and 5-year progression-free survival rates were 90.7% and 88.7% respectively, and the 3-year and 5-year overall survival rates were 92.8% and 90.7% respectively. Tumor budding status was an independent risk factor affecting patient recurrence (hazard ratio=3.375, 95% confidence interval: 1.060-10.741, P=0.039), patients with low-grade tumor budding had better prognosis, and those with medium or high-grade tumor budding had poor prognosis. Conclusion: For dMMR colorectal cancer patients, tumor budding status is an independent risk factor for recurrence.

Highest fusion performance without harmful edge energy bursts in tokamak.

The path of tokamak fusion and International thermonuclear experimental reactor (ITER) is maintaining high-performance plasma to produce sufficient fusion power. This effort is hindered by the transient energy burst arising from the instabilities at the boundary of plasmas. Conventional 3D magnetic perturbations used to suppress these instabilities often degrade fusion performance and increase the risk of other instabilities. This study presents an innovative 3D field optimization approach that leverages machine learning and real-time adaptability to overcome these challenges. Implemented in the DIII-D and KSTAR tokamaks, this method has consistently achieved reactor-relevant core confinement and the highest fusion performance without triggering damaging bursts. This is enabled by advances in the physics understanding of self-organized transport in the plasma edge and machine learning techniques to optimize the 3D field spectrum. The success of automated, real-time adaptive control of such complex systems paves the way for maximizing fusion efficiency in ITER and beyond while minimizing damage to device components.

MRI-based bone marrow radiomics for predicting cytogenetic abnormalities in multiple myeloma.

AIM: To develop a radiomics signature applied to magnetic resonance imaging (MRI)-images to predict cytogenetic abnormalities in multiple myeloma (MM). MATERIALS AND METHODS: Patients with newly diagnosed MM were enrolled retrospectively from March 2019 to September 2022. They were categorised into the high-risk cytogenetics (HRC) group and standard-risk cytogenetics (SRC) group. The patients were allocated randomly at a ratio of 7:3 into training and validation cohorts. Volumes of interest (VOI) was drawn manually on fat suppression T2-weighted imaging (FS-T2WI) and copied to the same location of the T1-weighted imaging (T1WI) sequence. Radiomics features were extracted from two sequences and selected by reproducibility and redundant analysis. The least absolute shrinkage selection operation (LASSO) algorithm was applied to build the radiomics signatures. The performance of the radiomics signatures to distinguish HRC with SRC was evaluated by ROC curves. The area under the curve (AUC), specificity, and sensitivity were also calculated. RESULTS: A total of 105 MM patients were enrolled in this study. The four and 11 most significant and relevant features were selected separately from T1WI and FS-T2WI sequences to build the radiomics signatures based on the training cohort. Compared to the T1WI sequence, the radiomics signature based on the FS-T2WI sequence achieved better performance with AUCs of 0.896 and 0.729 in the training and validation cohorts respectively. A sensitivity of 0.833, specificity of 0.667, and Youden index of 0.500 were achieved for the FS-T2WI radiomics signature in the validation cohort. CONCLUSIONS: The radiomics signature based on MRI provides a non-invasive and convenient tool to predict cytogenetic abnormalities in MM patients.

Experimental Validation of a Kinetic Ballooning Mode in High-Performance High-Bootstrap Current Fraction Fusion Plasmas.

We report the observation of a set of coherent high frequency electromagnetic fluctuations that leads to a turbulence induced self-regulating phenomenon in the DIII-D high bootstrap current fraction plasma. The fluctuations have frequency of 130-220 kHz, the poloidal wavelength and phase velocity are 16-30 m^{-1} and ∼30 km/s, respectively, in the outboard midplane with the estimated toroidal mode number n∼5-9. The fluctuations are located in the internal transport barrier (ITB) region at large radius and are experimentally validated to be kinetic ballooning modes (KBM). Quasilinear estimation predicts the KBM to be able to drive experimental particle flux and non-negligible thermal flux, suggesting its significant role in regulating the ITB saturation.

Discriminating minimal residual disease status in multiple myeloma based on MRI: utility of radiomics and comparison of machine-learning methods.

AIM: To explore the possibility of discriminating minimal residual disease (MRD) status in multiple myeloma (MM) based on magnetic resonance imaging (MRI) and identify optimal machine-learning methods to optimise the clinical treatment regimen. MATERIALS AND METHODS: A total of 83 patients were analysed retrospectively. They were divided randomly into training and validation cohorts. The regions of interest were segmented and radiomics features were extracted and analysed on two sequences, including T1-weighted imaging (WI) and fat saturated (FS)-T2WI, and then radiomics models were built in the training cohort and evaluated in the validation cohort. Clinical characteristics were calculated to build a traditional model. A combined model was also built using the clinical characteristics and radiomics features. Classification accuracy was assessed using area under the curve (AUC) and F1 score. RESULTS: In the training cohort, only the bone marrow (BM) infiltrate ratio (p=0.005) was retained after univariate and multivariable logistic regression analysis. In T1WI, the linear support vector machine (SVM) achieved the best performance compared to other classifiers, with AUCs of 0.811 and 0.708 and F1 scores of 0.792 and 0.696 in the training and validation cohorts, respectively. Similarly, in FS-T2WI sequence, linear SVM achieved the best performance with AUCs of 0.833 and 0.800 and F1 score of 0.833 and 0.800. The combined model constructed by the FS-T2WI-linear SVM and BM infiltrate ratio outperformed the traditional model (p=0.050 and 0.012, Delong test), but showed no significant difference compared with the radiomics model (p=0.798 and 0.855). CONCLUSION: The linear SVM-based machine-learning method can offer a non-invasive tool for discriminating MRD status in MM.

Pembrolizumab monotherapy versus chemotherapy in platinum-pretreated, recurrent or metastatic nasopharyngeal cancer (KEYNOTE-122): an open-label, randomized, phase III trial.

BACKGROUND: Pembrolizumab previously demonstrated robust antitumor activity and manageable safety in a phase Ib study of patients with heavily pretreated, programmed death ligand 1 (PD-L1)-positive, recurrent or metastatic nasopharyngeal carcinoma (NPC). The phase III KEYNOTE-122 study was conducted to further evaluate pembrolizumab versus chemotherapy in patients with platinum-pretreated, recurrent and/or metastatic NPC. Final analysis results are presented. PATIENTS AND METHODS: KEYNOTE-122 was an open-label, randomized study conducted at 29 sites, globally. Participants with platinum-pretreated recurrent and/or metastatic NPC were randomly assigned (1 : 1) to pembrolizumab or chemotherapy with capecitabine, gemcitabine, or docetaxel. Randomization was stratified by liver metastasis (present versus absent). The primary endpoint was overall survival (OS), analyzed in the intention-to-treat population using the stratified log-rank test (superiority threshold, one-sided P = 0.0187). Safety was assessed in the as-treated population. RESULTS: Between 5 May 2016 and 28 May 2018, 233 participants were randomly assigned to treatment (pembrolizumab, n = 117; chemotherapy, n = 116); Most participants (86.7%) received study treatment in the second-line or later setting. Median time from randomization to data cut-off (30 November 2020) was 45.1 months (interquartile range, 39.0-48.8 months). Median OS was 17.2 months [95% confidence interval (CI) 11.7-22.9 months] with pembrolizumab and 15.3 months (95% CI 10.9-18.1 months) with chemotherapy [hazard ratio, 0.90 (95% CI 0.67-1.19; P = 0.2262)]. Grade 3-5 treatment-related adverse events occurred in 12 of 116 participants (10.3%) with pembrolizumab and 49 of 112 participants (43.8%) with chemotherapy. Three treatment-related deaths occurred: 1 participant (0.9%) with pembrolizumab (pneumonitis) and 2 (1.8%) with chemotherapy (pneumonia, intracranial hemorrhage). CONCLUSION: Pembrolizumab did not significantly improve OS compared with chemotherapy in participants with platinum-pretreated recurrent and/or metastatic NPC but did have manageable safety and a lower incidence of treatment-related adverse events.

Improved Particle Confinement with Resonant Magnetic Perturbations in DIII-D Tokamak H-Mode Plasmas.

Experiments on the DIII-D tokamak have identified a novel regime in which applied resonant magnetic perturbations (RMPs) increase the particle confinement and overall performance. This Letter details a robust range of counter-current rotation over which RMPs cause this density pump-in effect for high confinement (H mode) plasmas. The pump in is shown to be caused by a reduction of the turbulent transport and to be correlated with a change in the sign of the induced neoclassical transport. This novel reversal of the RMP induced transport has the potential to significantly improve reactor relevant, three-dimensional magnetic confinement scenarios.

Evaluation of a new DIII-D Doppler backscattering system for higher wavenumber measurement and signal enhancement.

The high density fluctuation poloidal wavenumber, kθ (kθ > 8 cm-1, kθρs > 5, ρs is the ion gyro radius using the ion sound velocity), measurement capability of a new Doppler backscattering (DBS) system at the DIII-D tokamak has been experimentally evaluated. In DBS, wavenumber (k) matching becomes more important at higher wavenumbers, owing to the exponential dependence of the measured signal loss factor on wave vector mismatch. Wave vector matching allows for the Bragg scattering condition to be satisfied, which minimizes the signal loss at higher k's. In the previous DBS system, without toroidal wave vector matching, the measured DBS signal-to-noise ratio at higher kθ (>8 cm-1) is substantially reduced, making it difficult to measure higher kθ turbulence. The new DBS system has been optimized to access higher wavenumber, kθ ≤ 20 cm-1, density turbulence measurement. The optimization hardware addresses fluctuation wave vector matching using toroidal steering of the launch mirror to produce a backscattered signal with improved intensity. The probe's sensitivity to high-k density fluctuations has been increased by approximately an order of magnitude compared to the old system that has been in use at DIII-D. Note that typical measurement locations are above or below the tokamak midplane on the low field side with normalized radial ranges of 0.5-1.0. The new DBS probe system with the toroidal matching of fluctuation wave vectors is thought to be critical to understanding high-k turbulent transport in fusion-relevant research at DIII-D.

Validating and optimizing mismatch tolerance of Doppler backscattering measurements with the beam model (invited).

We use the beam model of Doppler backscattering (DBS), which was previously derived from beam tracing and the reciprocity theorem, to shed light on mismatch attenuation. This attenuation of the backscattered signal occurs when the wavevector of the probe beam's electric field is not in the plane perpendicular to the magnetic field. Correcting for this effect is important for determining the amplitude of the actual density fluctuations. Previous preliminary comparisons between the model and Mega-Ampere Spherical Tokamak (MAST) plasmas were promising. In this work, we quantitatively account for this effect on DIII-D, a conventional tokamak. We compare the predicted and measured mismatch attenuation in various DIII-D, MAST, and MAST-U plasmas, showing that the beam model is applicable in a wide variety of situations. Finally, we performed a preliminary parameter sweep and found that the mismatch tolerance can be improved by optimizing the probe beam's width and curvature at launch. This is potentially a design consideration for new DBS systems.

ß-Nuclear-Recoil Correlation from

We report the first precise measurement of a ß-recoil correlation from a radioactive noble gas (^{6}He) confined via a magneto-optical trap. The measurement is motivated by the search for exotic tensor-type contributions to the charged weak current. Interpreted as tensor currents with right-handed neutrinos, the measurements yield |C_{T}/C_{A}|^{2}≤0.022 (90% confidence limit, C.L.). On the other hand, for left-handed neutrinos the limits are 0.007

Anesthetic management for the peripartum care of women with Fontan physiology.

BACKGROUND: As outcomes for surgical palliation have improved, women with single ventricle congenital heart disease are surviving into their reproductive years and may become pregnant. The cardiovascular changes of pregnancy may stress the Fontan circulation and pose significant risk to the mother and fetus. METHODS: Pregnant women with Fontan physiology were identified from the Ahmanson/UCLA Adult Congenital Heart Disease Center database. A total of 37 pregnancies were identified between 2000 and 2019. Twenty live births from 19 patients were reviewed and compared for cardiac history, obstetric history, anesthetic management and cardiovascular outcomes. RESULTS: Median gestational age at delivery was 35 weeks. Ten of 20 births were by cesarean delivery. An epidural technique was used as the primary anesthetic for 19 deliveries and general anesthesia was used for one cesarean delivery. An arterial line was placed in the peripartum period for three deliveries. Central venous access was established in the peripartum period for one patient. The mean blood loss for cesarean deliveries was 626 mL (range 240-1200 mL). The mean net peri-operative intake/output was positive 93.5 mL. Three patients were briefly transferred to the intensive care unit postpartum for higher level monitoring and care. CONCLUSION: Epidural anesthesia is safe and effective for both vaginal and cesarean deliveries. Judicious fluid management is critical in minimizing postpartum cardiovascular complications. Many patients do not require a higher level of care, invasive monitoring or central venous access during the peripartum period.

Multiscale Chirping Modes Driven by Thermal Ions in a Plasma with Reactor-Relevant Ion Temperature.

A thermal ion driven bursting instability with rapid frequency chirping, considered as an Alfvénic ion temperature gradient mode, has been observed in plasmas having reactor-relevant temperature in the DIII-D tokamak. The modes are excited over a wide spatial range from macroscopic device size to microturbulence size and the perturbation energy propagates across multiple spatial scales. The radial mode structure is able to expand from local to global in ∼0.1 ms and it causes magnetic topology changes in the plasma edge, which can lead to a minor disruption event. Since the mode is typically observed in the high ion temperature ≳10 keV and high-ß plasma regime, the manifestation of the mode in future reactors should be studied with development of mitigation strategies, if needed. This is the first observation of destabilization of the Alfvén continuum caused by the compressibility of ions with reactor-relevant ion temperature.

Ray-tracing analysis for cross-polarization scattering diagnostic on MAST-upgrade spherical tokamak.

A combined Doppler backscattering/cross-polarization scattering (DBS/CPS) system is being deployed on MAST-U for simultaneous measurements of local density turbulence, turbulence flows, and magnetic turbulence. In this design, CPS shares the probing beam with the DBS and uses a separate parallel-viewing receiver system. In this study, we utilize a modified GENRAY 3D ray-tracing code to simulate the propagation of the probing and scattered beams. The contributions of different scattering locations along the entire beam trajectories are considered, and the corresponding local B̃ wavenumbers are estimated using the wavevector matching criterion. The wavenumber ranges of the local B̃ that are detectable to the CPS system are explored for simulated L- and H-mode plasmas.

Discovery of New Imidazo[2,1-b]thiazole Derivatives as Potent Pan-RAF Inhibitors with Promising In Vitro and In Vivo Anti-melanoma Activity.

BRAF is an important component of MAPK cascade. Mutation of BRAF, in particular V600E, leads to hyperactivation of the MAPK pathway and uncontrolled cellular growth. Resistance to selective inhibitors of mutated BRAF is a major obstacle against treatment of many cancer types. In this work, a series of new (imidazo[2,1-b]thiazol-5-yl)pyrimidine derivatives possessing a terminal sulfonamide moiety were synthesized. Pan-RAF inhibitory effect of the new series was investigated, and structure-activity relationship is discussed. Antiproliferative activity of the target compounds was tested against the NCI-60 cell line panel. The most active compounds were further tested to obtain their IC50 values against cancer cells. Compound 27c with terminal open chain sulfonamide and 38a with a cyclic sulfamide moiety showed the highest activity in enzymatic and cellular assay, and both compounds were able to inhibit phosphorylation of MEK and ERK. Compound 38a was selected for testing its in vivo activity against melanoma. Cellular and animal activities are reported.

Dual-energy CT for differentiating early glottic squamous cell carcinoma from chronic inflammation and leucoplakia of vocal cord: comparison with simulated conventional 120 kVp CT.

AIM: To evaluate the value of dual-energy (DE) computed tomography (CT) in discriminating early glottic squamous cell carcinoma (eGSCC) from chronic inflammation and leucoplakia of the vocal cord, and to compare the diagnostic efficiency of DECT with that of simulated conventional 120 kVp CT. MATERIALS AND METHODS: Seventy patients with glottic lesions confirmed by histopathology (38 cases with eGSCC, 11 cases with chronic inflammation, 21 cases with leucoplakia) were enrolled in this prospective study. The DECT-derived parameters were measured and compared using independent sample t-test. Receiver operating characteristic (ROC) curve was performed to evaluate the diagnostic performance, and comparison of the area under the ROC curve (AUC) was made using the Z test to further select the best diagnostic parameters. RESULTS: Significantly higher iodine concentration (IC), normalised IC (NIC), effective atomic number (Zeff), 40-100 keV (20 keV-interval), slope(k), and Mix-0.3 values were found in eGSCC than those in chronic inflammation, leucoplakia, and inflammation + leucoplakia (all p<0.05). Compared with attenuation measurement of simulated conventional 120 kVp CT, the NIC, 60 keV values derived from DECT showed significantly higher AUC in discriminating these glottic lesions (p<0.05). CONCLUSIONS: DECT is more accurate for differentiating eGSCC from chronic inflammation and leucoplakia when compared with simulated conventional 120 kVp CT.

Identification of CD137- and CD137L-Expressing Cells in EL-4 Tumor.

The tumor microenvironment (TME) contains noncancerous cells such as various types of immune cells and fibroblasts. Cancer cells direct these stromal cells to create a microenvironment favorable for tumor growth and intercellular interactions have a critical role in this process. In established tumors, interactions between CD137 and its ligand (CD137L) contribute to tumor immune evasion and tumor growth. Therefore, it is important to identify cells expressing CD137 and CD137L within tumors. In this chapter, we will introduce a simple, powerful method of analyzing CD137- and CD137L-expressing tumor cells using Fluorescence-activated cell sorting.