tbuckley/cabot-search huggingface dataset:
Downregulation of E-selectin and contributions to immune restraining in prostate cancer.
Authors: Ida Deichaite, Andrew Elliott, Ahmed Shabaik, Leisa Sutton, Stephanie Weaver, Miki Haraguchi, Daniel M. Geynisman, Shuanzeng Wei, Napoleone Ferrara, Fotis Asimakopoulos, Pablo Tamayo
Journal: Journal of Clinical Oncology (2025)

257 Background: Immune surveillance in prostate cancer (PCa) relies on leukocyte trafficking into target tissues, a process mediated by endothelial adhesion molecules. This study investigates the role of E-selectin (SELE) in PCa immune evasion and patient outcomes. Methods: We analyzed transcriptomic data from 7,523 PCa samples (4,768 localized; 2,755 metastatic) molecularly profiled at Caris Life Sciences to assess SELE expression. Correlations between TNF and adhesion molecule expression were examined in normal prostate and PCa tissues. Survival analysis was performed based on SELE expression levels. Immunohistochemistry was conducted to evaluate SELE protein expression in tumor, benign prostatic hyperplasia (BPH), and stromal samples. Results: SELE was significantly upregulated in localized PCa samples compared to metastases (SELE: 0.83 vs 0.47 TPM, p&lt;0.001), along with SELP (P-selectin) (3.15 vs 1.29 TPM, p&lt;0.0001), ICAM1 (5.05 vs 3.70, P&lt;0.0001) and VCAM1 (7.10 vs 5.41, P&lt;0.001), while TNF expression was similar (0.48 vs 0.43 TPM, P&lt;0.001). TNF positively correlated with SELE, with a stronger correlation observed in metastatic vs localized PCa samples, suggesting altered transcriptional regulation. High expression of SELE was associated with improved survival among patients with localized PCa (HR=0.61, p&lt;0.0001), with no significant difference observed among those with metastatic PCa (HR=0.90, p=0.153). Among those with localized PCa, high expression of SELP was also associated with improved survival (HR=0.75, p&lt;0.001), while worse overall survival was associated with high expression of ICAM1 (HR=1.58, p&lt;0.0001), VCAM1 (HR=1.73, p&lt;0.0001), and TNF (HR=1.23, p=0.004). Combined high SELE/low TNF demonstrated an enhanced survival effect compared to low SELE/high TNF (HR=0.44, p&lt;0.001). Conclusions: Our findings suggest that downregulation of SELE in PCa contributes to tumor "coldness" by potentially reducing anti-tumor immune cell infiltration. This mechanism may explain the limited efficacy of immune checkpoint inhibitors in PCa. The strong association between SELE expression and improved survival highlights their potential for prognostic biomarker and therapeutic target in PCa.
Association of androgen deprivation therapy and acute kidney injury in patients with prostate cancer: A systematic review and meta-analysis.
Authors: Gustavo Franco Carvalhal, Iago Pires, Renan Yuji Ura Sudo, Marília Oberto da Silva Gobbo, Nilson Marquardt Filho
Journal: Journal of Clinical Oncology (2025)

111 Background: Androgen deprivation therapy (ADT) has been associated with cardiovascular risk in prostate cancer patients. Thus, we performed a systematic review and meta-analysis to assess the incidence of acute kidney injury (AKI) in prostate cancer patients under ADT. Methods: PubMed, Embase, and Cochrane Library were searched from inception to October 2024. A random-effects model was employed to compute mean differences for continuous endpoints. Heterogeneity was evaluated by prediction interval and I-squared statistics. All statistical analysis was conducted using R software 4.4.1. GRADE approach rated the certainty of the evidence and the results were reported following the PRISMA statement guidelines. Results: Four studies involving 72,980 patients with a mean age of 73.5 years were included. Over a mean follow-up of 6.7 years, ADT was associated with an increase in the AKI incidence in prostate cancer patients compared to patients not receiving ADT (RR 1.34; 95% CI 1.13-1.58; p&lt;0.001). Among patients who developed AKI while receiving ADT, the use of GnRH agonists was not associated with AKI incidence (RR 4.32; 95% CI 0.60-30.97; p=0.146). Similarly, when comparing AKI risk between patients on GnRH agonists alone and those without ADT, no statistically significant difference was found (RR 1.24; 95% CI 0.73-2.11; p=0.424). Orchiectomized patients had a lower AKI incidence than GnRH agonist users (RR 1.16; 95% CI 1.04-1.3; p=0.009). All studies were limited by retrospective designs, introducing potential selection and therapeutic bias. Conclusions: In this meta-analysis, ADT was associated with an increased risk of AKI. No statistical association was found between GnRH agonist use and AKI. Orchiectomy presented a lower AKI risk compared to GnRH agonists. Further investigations, including post hoc analysis of randomized controlled trials, are warranted to confirm these findings. Characteristics of the included studies. Study Sample size (n) Mean age (years) ADT modality Control group AKI incidence (ADT) AKI incidence (control) Hazard ratio for GnRH use (95% CI) – sensitivity analyses Follow-up (years) Gandaglia 2014 31,408 78.6 GnRH agonist and Bilateral orchiectomy No ADT 30.7% 24.9% 1.73 (1.62-1.85) 10 Cardwell 2021 10,751 69.2 GnRH agonists, GnRH antagonist, oral antiandrogens, estrogens and orchiectomy No ADT 6.1% 5.2% 1.09 (0.88-1.34) 3.9 Sherer 2021 27,868 66 GnRH agonists, oral antiandrogens, and GnRH antagonist No ADT +Radiotherapy 10.5% 7.9% 1.25 (1.13-1.37) a 8.8 Lapi 2013 2,953 80.2 GnRH agonists, oral antiandrogens, GnRH agonists + oral antiandrogens, bilateral orchiectomy, estrogens, other combinations No ADT 9.2% 4.5% ≈ 1.54 (1.17-2.15) b / ≈ 1.04 (1.27-1.46) c 4.1 a Sensitivity analysis of all ADT modalities. b Adjusted analysis of current ADT modalities. c Adjusted analysis of past ADT modalities.
Lewis Y antigen as a novel target for CAR (chimeric antigen receptor) T-cell therapy in patients with neuroendocrine prostate cancer.
Authors: Weronika Kulakowska, Renea Taylor, Weranja Ranasinghe, Phillip K. Darcy, Joseph Trapani, Gail Risbridger
Journal: Journal of Clinical Oncology (2025)

217 Background: Neuroendocrine prostate cancers (NEPC) currently have no effective therapies. While CAR (Chimeric Antigen Receptor) T cell therapies targeting PSMA and PSCA receptors are currently in phase 1/2 studies in metastatic castrate-resistant prostate cancer (mCRPC), antigen targets for NEPC remain limited. Lewis Y antigen (LeY) is an oncofetal antigen expressed only in adult tumour cells and is considered a target for CAR T cell therapy in haematological, lung, ovarian and colon cancer. We previously found that LeY is a promising target for CAR T cell therapy in prostate cancer and that preconditioning LeY-directed CAR T cells with carboplatin further enhances tumour responses in mCRPC. We investigated if LeY can be used as a novel CAR T cell target for NEPC. Methods: The expression of the Lewis Y antigen was assessed in our patient-derived prostate cancer xenograft collection using immunohistochemistry (IHC). To assess the efficacy of LeY-CAR T cells, we used specimens established from a patient (Patient 508) with NEPC who had incurable metastatic disease and failed standard treatments. We generated CAR T cells from his peripheral blood mononuclear cells (PBMCs) to test their specificity and efficacy in vitro against established cell lines. Results: In our MURAL PDX collection of 59 prostate tumours, 81% (9/11) NEPCs expressed LeY antigen on IHC. Next, we successfully produced anti-LeY CAR T cells from the patient’s PBMCs using retroviral transduction. Flow cytometry verified efficient transduction of the CAR constructs. Previous studies found that a 1:1 ratio of CD4 + :CD8 + T cells improved outcomes following CAR T cell therapy 5,6 , so we further phenotyped patient T cells by flow cytometry. The CD4 + :CD8 + T cell ratio was nearly 1:1 (51.7% and 41.4% of total T cells, respectively). Next, we used an immunobead assay to investigate CAR-T specificity in releasing proinflammatory cytokines. Significant cytokine production was observed after a 4-hour co-culture with LeY+ human ovarian cancer cell line, OVCAR3, vs co-culture with control LeY- MDA-MB435 cells (p=0.0004), demonstrating the specificity of the CAR T cells.Lastly, we showed that patient CAR T cells effectively killed LeY+ cells (OVCAR3), but not control LeY- cells (MDA-MB435; p&lt;0.0001). Tumour cell death was measured by the amount of released chromium following 16-hour co-culture. CAR T cells killed LeY+ target cells more effectively than their non-transduced equivalents at a range of effector-to-target ratios, with up to 15-fold increase in cell death. Conclusions: Our preclinical studies show that most NEPC tumors express the LeY antigen and that patient-derived CAR T cells specifically kill those cells. These findings identified a potential CAR T treatment target for NEPC for a phase 1/2 study.
PUNCH01: Interim results from a phase II study of intra-arterial chemotherapy (IAC) combined with tislelizumab and bacillus Calmette-Guerin (BCG) in high-risk non-muscle-invasive bladder cancer (HR NMIBC).
Authors: Zongren Wang, Bin Huang, Cheng Luo, Yuxi Wu, Jiahao Lei, Lingwu Chen, Junxing Chen
Journal: Journal of Clinical Oncology (2025)

767 Background: Our study was established to evaluate the efficacy and safety of IAC combined with tislelizumab and BCG as a bladder-preserving treatment for HR NMIBC pts. Methods: This open-label, single arm phase II study enrolled BCG-naïve HR NMIBC pts with papillary tumors (high-grade Ta or T1 tumors). Firstly, the papillary tumors should be removed all visible lesions by TURBT. Secondly, angiographic catheter was placed into the internal iliac arteries with Seldinger’s percutaneous technique, cisplatin (60 mg/m 2 ) and epirubicin (50 mg/m 2 ) were administered arterially in day 1 (D1), every 3 weeks for 2-4 cycles. And pts received tislelizumab 200 mg ivgtt in D1, every 3 weeks for 2-4 cycles. Finally, pts received 18 instillations of BCG plus at least 8 cycles of tislelizumab (200 mg ivgtt, every 3 weeks). Specifically, pts were started on an induction course of BCG with 6 instillations every week, followed by maintenance with 3 instillations every 2 weeks and 9 instillations every 4 weeks. The primary end point was disease-free survival(DFS) rate at 12 months. Secondary end points were bladder-preservation rate, OS and safety. Our study estimated a DFS rate at 12 months was no less than 55% and the study would enroll 29 pts. Results: By Jul. 2024, 23 eligible pts were enrolled. Twenty-two pts were analyzed (male 90.9%; median age 61 years(37-80); pure TCC 80.0%; median tumor size 3.0 cm (0.4-8.0); multiple papillary tumours=72.7%; high-gradeTa=54.5%, T1=45.5%). Median follow-up was 11.4 months (6.0-40.3), the mean number of IAC cycles was 2.7, mean number of tislelizumab cycles was 8.3, and the median BCG instillations was 10 (6-18). The DFS rate at 12month was 100.0% (95%CI, 63.8%-100%). The bladder-preservation rate at 12 months was 100% (95%CI,100%-100%). The OS rate at 12 months was 100% (95%CI, 100%-100%). 18 pts experienced treatment related adverse events, including nausea (n=6, G2), neutropenia (n=4, G2), fatigue (n=3, G2), increased AST/ALT (n=3,G2), fever (n=2, G3) and myalgia (n=1, G2). Conclusions: Our interim results supported the use of IAC combined with tislelizumab and BCG as a promising bladder-preserving strategy for HR NMIBC pts. Clinical trial information: ChiCTR2200067156 .
Evaluating the efficacy of cabozantinib in patients with advanced renal cell carcinoma with bone metastasis: An open-label phase 2 study.
Authors: Fumiya Hongo, Yasutomo Nakai, Masahiro Nozawa, Taigo Kato, Sadanori Kamikawa, Satoshi Tamada, Kaori Yamada, Junpei Soeda, Ryoichi Tsubouchi, Tsuyoshi Osaka, Hirotsugu Uemura
Journal: Journal of Clinical Oncology (2025)

535 Background: Bone metastasis negatively impacts patients with advanced renal cell carcinoma (aRCC), leading to poor prognosis and quality of life. Some tyrosine kinase inhibitors, including cabozantinib, have been used as standard care for aRCC. However, there have been no reports demonstrating the effects of cabozantinib on bone metastasis. Here, we report the clinical effects of cabozantinib on bone metastasis in patients with aRCC. Methods: Patients with aRCC who had at least one measurable bone target lesion were enrolled. Patients received cabozantinib 60 mg once daily until disease progression or intolerable toxicity. The primary endpoint was objective response rate (ORR) of bone target lesions based on independent review committee (IRC) assessment using the MD Anderson Cancer Center (MDA) criteria, which are the response criteria specific to bone metastases. Key secondary endpoints included disease control rate (DCR), bone metastasis-free survival (BMFS), progression-free survival (PFS), overall survival (OS), frequency of symptomatic skeletal events (SSE) and safety. Results: In total, 31 patients were enrolled, with a median age of 70.0 years, and most patients (77.4%) had a history of systemic treatments for aRCC. All patients had bone metastasis. The ORR of bone target lesions by IRC-assessed MDA criteria was 6.5% (90% CI: 1.2–18.9), with a disease control rate (DCR) of 90.3% (90% CI: 76.8–97.3). No progressive disease was observed. The median BMFS was not reached (95% CI: 11.5–NR). The median PFS and OS were 11.9 (95% CI: 5.7–NR) months and 24.9 (95% CI: 19.1–NR) months, respectively. Three patients (9.7%) experienced SSE. No new safety concerns were identified. Conclusions: Cabozantinib demonstrated favorable clinical effects on bone metastasis in patients with aRCC, as suggested by a high DCR. Our results may provide useful insights for selecting optimal treatments for the management of aRCC with bone metastasis. Clinical trial information: jRCTs031210220 .
Impact of the 2012 and 2018 USPSTF statements on prostate cancer screening and metastatic rates in Kaiser Permanente Northern California.
Authors: Joseph Presti, Brandon Horton, Stacey Alexeeff, Stephanie Prausnitz, Andrew Avins
Journal: Journal of Clinical Oncology (2025)

359 Background: To assess how the United States Preventive Services Task Force (USPSTF) Prostate Cancer Screening Statements of 2012 (Grade D - “recommends against”) and 2018 (Grade C - “selectively offering...based on professional judgment and patient preferences”) influenced race-specific rates of PSA screening and metastatic cancer at presentation among screen-eligible men in Kaiser Permanente Northern California. Methods: This is a retrospective study from 2006 to 2022, in screen-eligible (ages 50-69), Kaiser Permanente Northern California members. We compared the race-specific rates of PSA screening and metastatic cancer at presentation before and after the changes in the USPSTF Statements. Results: In 2006 there were 324,950 screen-eligible men (11% Black, 17% Asian, 73% White). In 2022 there were 434,705 screen-eligible men (11% Black, 27% Asian, 63% White). Race-specific, annual screening and metastatic rates are shown (Table). Following the 2012 USPSTF statement, all races experienced similar declines in screening and an increase in metastatic rates which was greatest among Black men. Following the 2018 statement, all races experienced similar increases in screening (with the exception of the time around the pandemic in 2020); yet as of 2022, the rate of metastatic cancer has continued to increase. Conclusions: The 2012 USPSTF Statement (Grade D) was associated with a decline in screening and an increase in metastatic rates among all races, yet was greatest among Black men, a high-risk group. Following the 2018 USPSTF Statement (Grade C), screening rates have increased yet metastatic rates continue to rise and remains greatest among Black men. Biennial race-specific screening and metastatic rates. 2006 2008 2010 2012 2014 2016 2018 2020 2022 Screening Rates(per 100,000 person-yrs) Asian 477 511 512 453 406 370 380 262 432 Black 441 452 468 398 364 328 338 255 381 White 438 461 455 398 354 315 329 242 384 Metastatic Rates(per 100,000 person-yrs) Asian 0.06 0.22 0.08 0.06 0.12 0.20 0.25 0.16 0.34 Black 0.44 0.34 0.33 0.31 0.66 0.76 0.85 0.72 1.18 White 0.26 0.23 0.19 0.17 0.30 0.31 0.42 0.48 0.73
Impact of physicians’ awareness of prostate-specific antigen doubling time (PSADT) on treatment (Tx) decisions in high-risk (HR) biochemically recurrent (BCR) prostate cancer (PC).
Authors: Alicia K. Morgans, Maelys Touya, Nader N. El-Chaar, Dina Elsouda, Krishnan Ramaswamy, Kelechi L. Adejumo, Danielle Gentile, Bruce A. Feinberg, Parisa Asgarisabet, Prathamesh Pathak, Stephen J. Freedland
Journal: Journal of Clinical Oncology (2025)

354 Background: PSADT is one of the strongest predictors of outcomes in patients (pts) with BCR PC and a criterion for HR BCR definition. As such, it is crucial to determine whether physicians are aware of pts’ PSADT and how this influences Tx in routine practice. We compared Tx patterns in pts with HR BCR whose PSADT was known (kPSADT) or unknown (uPSADT) by the physician. Methods: This physician-abstracted chart review used data of pts with HR BCR from the Cardinal Health Oncology Provider Extended Network (2018–2020) in the US. HR BCR definition: PSADT ≤9 months (mo) with PSA at or above the threshold per the EMBARK trial. Follow-up was from the index date (date on which HR BCR definition was met) until disease progression, last follow-up, or death through 2022. Physicians reported PSADT in case report forms (CRFs) using doubling time from labs, clinical judgement, or an online calculator (kPSADT). If not provided in the CRF, PSADT was calculated retrospectively based on PSA values up to the index date that the physician had entered in the CRF (uPSADT). We analyzed time to treatment after index via the Kaplan–Meier method. Results: Among 284 pts with HR BCR, median time from initial PC diagnosis to the end of follow-up was 39.1 mo; most pts had kPSADT). There were differences between in age, time from localized PC diagnosis to BCR, Gleason score, and PSA at initial diagnosis and at BCR (Table). A higher proportion of pts with uPSADT had a fast PSADT (≤3 mo) (61% vs 20%, P &lt; 0.001). A higher proportion of pts with kPSADT (64%) vs uPSADT (17%) received Tx within 60 days after index, with a shorter median time to Tx (1.0 vs 6.7 mo; HR: 3.4, 95% CI: 2.6–4.4, P &lt; 0.0001). Conclusions: Most physicians did not know their pts’ PSADT. Even though pts with HR BCR PC who had kPSADT were older and had slower PSADT, they were over three times more likely to receive Tx vs pts with uPSADT. The results suggest that many pts with HR BCR PC may be missed in clinical practice, which limits these pts’ opportunity to receive guideline-concordant Tx to delay progression. Characteristics of index kPSADTn = 104 uPSADTn = 180 P value Age (years), mean (SD) 70.0 (7.6) 65.6 (7.0) &lt;0.001 Primary definitive PC Tx, n (%) Radiotherapy 28 (27) 51 (28) Prostatectomy 76 (73) 129 (72) Time from localized PC diagnosis to BCR ≤2 years, n (%) 97 (93) 143 (79) 0.002 Gleason score ≥8, n (%) 76 (73) 81 (45) &lt;0.001 PSA before initial localized PC diagnosis (ng/mL), median (IQR) 9.0 (6.7) 7.9 (8.6) 0.019 PSA at BCR (ng/mL), median (IQR) 3.4 (9.0) 2.6 (2.8) &lt;0.001
Vitamin E (300 mg) in the treatment of MASH: A multi-center, randomized, double-blind, placebo-controlled study
Authors: Yu Song, Wenjing Ni, Minghua Zheng, Huiping Sheng, Jing Wang, Shilong Xie, YongFeng Yang, Xiaoling Chi, Jinjun Chen, Fangping He, Xiaotang Fan, Yuqiang Mi, Jing Zhang, Bingyuan Wang, Lang Bai, Wen Xie, Bihui Zhong, Yee Hui Yeo, Fajuan Rui, Shufei Zang, Jie Li, Junping Shi
Journal: Cell Reports Medicine (2025)
Profiling the gut microbiota to assess infection risk in <i>Klebsiella pneumoniae</i> -colonized patients
Authors: Flavio De Maio, Delia Mercedes Bianco, Giulia Santarelli, Roberto Rosato, Francesca Romana Monzo, Barbara Fiori, Maurizio Sanguinetti, Brunella Posteraro
Journal: Gut Microbes (2025)

Vornhagen et al. introduced a model combining gut microbiota structure and Klebsiella pneumoniae genotype to assess infection risk in K. pneumoniae-colonized patients. Building on their findings, we investigated the gut microbiota composition and K. pneumoniae genotype in 16 colonized patients, five of whom had bloodstream infections at the time of fecal sampling. Importantly, we did not apply the original machine learning model due to the small sample size of our cohort. Instead, we explored the distribution of key antimicrobial resistance and stress resistance genes and analyzed gut community structure based on amplicon sequence variants (ASVs) of the V3–V4 16S rRNA region. Notably, distinct gene profiles were observed in both infected and non-infected patients, and three patients without bloodstream infections showed no detectable Klebsiella ASVs despite microbiological confirmation of colonization. These findings highlight the need to integrate gut microbiota composition data into infection risk assessment and address limitations in taxonomic resolution and sample size. Future studies should aim to develop streamlined tools for clinical application in K. pneumoniae-colonized patients.
Concordance of circulating tumor DNA and imaging surveillance in patients with urothelial carcinoma and renal cell carcinoma post-immunotherapy.
Authors: Lingbin Meng, Katharine A. Collier, Elshad Hasanov, Amir Mortazavi, Steven K. Clinton, Peng Wang, Danielle Elise Zimmerman, Fuat Bicer Bicer, Timothy D. Gauntner, Edmund Folefac, Paul Monk, Yuanquan Yang
Journal: Journal of Clinical Oncology (2025)

597 Background: Early detection of recurrence in urothelial carcinoma (UC) and renal cell carcinoma (RCC) may improve patient outcomes. Conventional imaging techniques may not identify early molecular relapses that precede clinical relapse. Circulating tumor DNA (ctDNA) has emerged as a promising biomarker for the early detection of disease relapse. This study aims to evaluate the concordance of molecular relapses by ctDNA and radiographic progression in patients with UC and RCC who are off immunotherapy due to intolerance of side effects or completion of treatment. Methods: We conducted a retrospective study of locally advanced/advanced UC and RCC patients who were treated at The Ohio State University James Cancer Hospital from November 2021 to September 2024. Patients who completed planned immunotherapy followed by imaging and ctDNA surveillance were included. ctDNA levels were measured using the Signatera tissue informed assay at intervals of 4 to 12 weeks. Imaging surveillance schedules were at the treating physician discretion. Patient demographics, clinical characteristics, and ctDNA levels were recorded and analyzed. Results: A total of 36 patients were included: muscle-invasive bladder cancer (MIBC, n = 10), metastatic urothelial carcinoma (mUC, n = 10), locally advanced RCC (n = 4), and metastatic RCC (mRCC, n = 12). The median follow-up was 39.5 weeks (range: 1–138 weeks), with a median age of 67.5 years (range: 41–83 years), and 72.2% were male. At the time of immunotherapy discontinuation, ctDNA was negative in all patients except one mRCC patient (ctDNA 0.95 MTM/mL). During surveillance, 9 patients (25%) - 5 mUC and 4 mRCC - became ctDNA-positive, of which, eight showed radiographic progression, while one mRCC patient (ctDNA 0.15 MTM/mL) did not. None of the 27 patients (75%) that continued to have negative ctDNA had radiographic progression. For the 8 patients with progression, the median time from stopping immunotherapy to ctDNA relapse was 17.5 weeks (range: 11–42 weeks). The median time from ctDNA relapse to imaging-confirmed progression was 22 weeks (range: 13–43 weeks). At progression, ctDNA levels ranged from 0.08 to 136.49 MTM/mL (median: 2.33 MTM/mL). Six of the 20 metastatic patients (30%) relapsed despite negative ctDNA at immunotherapy discontinuation. Conclusions: ctDNA positivity occurs much earlier and is highly concordant with radiographic progression in patients with locally advanced/advanced UC and RCC under post-immunotherapy surveillance. These findings suggest that ctDNA is a promising tool for early disease relapse detection in these patients. Further studies are warranted to validate these results and establish standardized ctDNA surveillance protocols.