tbuckley/cabot-search huggingface dataset:
Pan-cancer γδ TCR analysis uncovers clonotype diversity and prognostic potential
Authors: Xiaoqing Yu, Li Song, Ling Cen, Biwei Cao, Ranran Tao, Yuanyuan Shen, Daniel Abate-Daga, Paulo C Rodriguez, Jose R Conejo-Garcia, Xuefeng Wang
Journal: Cell Reports Medicine (2024)

Gamma-delta T cells (γδ T cells) play a crucial role in both innate and adaptive immunity within tumors, yet their presence and prognostic value in cancer remain underexplored. This study presents a large-scale analysis of γδ T cell receptor (γδ TCR) reads from 11,000 tumor samples spanning 33 cancer types, utilizing the TRUST4 algorithm. Our findings reveal extensive diversity in γδ TCR clonality and gene expression, underscoring the potential of γδ T cells as prognostic biomarkers in various cancers. We further demonstrate the utility of TCR gamma (TRG) and delta (TRD) gene expression from standard RNA-sequencing (RNA-seq) data. This comprehensive dataset offers a valuable resource for advancing γδ T cell research, with implications for enhanced immunotherapy approaches or alternative therapeutic strategies. Additionally, our centralized database supports translational research into the therapeutic significance of γδ T cells.
Clinical outcomes of patients with HR-positive advanced breast cancer treated with eribulin: A retrospective multicenter study from China.
Authors: Aodi Li, Zheng Lv, Zhiqiang Zhang, Jing Shi, Lei Zhao, Lili Cao, Yuee Teng
Journal: Journal of Clinical Oncology (2024)

e13010 Background: Approximately 75% of patients with metastatic breast cancer are hormone receptor positive (HR+)/ human epidermal growth factor receptor 2 negative (HER2-) and are treated with endocrine therapy based on subtype. However, the high rate of resistance to endocrine therapy requires switching to new approaches, including chemotherapy. Eribulin is a novel synthetic analog of halichondrin B that acts as a non-taxane microtubule dynamics inhibitor and inhibits the G2-M growth phase. In this study, we retrospectively assessed the clinical outcomes of Chinese patients with HR+ advanced breast cancer (ABC) who received eribulin. Methods: The study included 62 patients with HR+/HER2– ABC in three Chinese institutions between August 2019 and August 2023. Socio-demographic, clinical, pathology, imaging, and therapy records were reviewed. Progression-free survival (PFS) and tumor response were evaluated. Results: A total of 62 patients were included. The median age was 50.0 years. Eribulin was used as a second, third, fourth and fifth or more therapy agent in 4 (6.5%), 23 (37.1%), 15 (24.2%) and 20 (32.3%) of ABC patients, respectively. 54.8% of the patients had previously used CDK4/6 inhibitors. Eribulin monotherapy and eribulin-based combination therapy were 59.7% and 40.3% of patients. The objective response rate (ORR) and disease control rate (DCR) were 21.0% (13/62) and 88.7% (55/62) overall. By number of lines of therapy, the less than or equal third line ORR was 33.3% and the greater than third line ORR was 11.4% ( p = 0.0577). The median progression-free survival (mPFS) of total population was 5.2 months (95% CI: 4.1–5.8). The mPFS was 6.1 and 4.1 months in the eribulin-based combination therapy group and eribulin monotherapy group ( p = 0.0219), respectively. By number of lines of therapy, the mPFS was 5.8 and 4.1 months in the less than or equal third line and greater than third line treatment ( p = 0.05), respectively. Whether CDK4/6i had been used in these ABC patients had no effect on PFS, which was 5.0 and 5.5 months, respectively. Conclusions: This retrospective study suggests that eribulin was effective in HR+ Chinese patients with ABC. The front-line and combined therapy of eribulin in HR+ ABC need further exploration.
T lymphocyte recruitment to melanoma brain tumors depends on distinct venous vessels
Authors: Julia M Messmer, Calvin Thommek, Manuel Piechutta, Varun Venkataramani, Rebekka Wehner, Dana Westphal, Marc Schubert, Chanté D Mayer, Maike Effern, Anna S Berghoff, Daniel Hinze, Iris Helfrich, Dirk Schadendorf, Wolfgang Wick, Michael Hölzel, Matthia A Karreman, Frank Winkler
Journal: Immunity (2024)

To improve immunotherapy for brain tumors, it is important to determine the principal intracranial site of T cell recruitment from the bloodstream and their intracranial route to brain tumors. Using intravital microscopy in mouse models of intracranial melanoma, we discovered that circulating T cells preferably adhered and extravasated at a distinct type of venous blood vessel in the tumor vicinity, peritumoral venous vessels (PVVs). Other vascular structures were excluded as alternative T cell routes to intracranial melanomas. Anti-PD-1/CTLA-4 immune checkpoint inhibitors increased intracranial T cell motility, facilitating migration from PVVs to the tumor and subsequently inhibiting intracranial tumor growth. The endothelial adhesion molecule ICAM-1 was particularly expressed on PVVs, and, in samples of human brain metastases, ICAM-1 positivity of PVV-like vessels correlated with intratumoral T cell infiltration. These findings uncover a distinct mechanism by which the immune system can access and control brain tumors and potentially influence other brain pathologies.
Addition of the MUC-1 vaccine tecemotide to neoadjuvant systemic therapy for patients with early breast cancer: Survival results from the prospective randomized ABCSG 34 trial.
Authors: Christian F. Singer, Dominik Hlauschek, Georg Pfeiler, Daniel Egle, Rupert Bartsch, Christoph Suppan, Angelika Pichler, Edgar Petru, Richard Greil, Margaretha Rudas, Michael Seifert, Andreas Petzer, Florian Fitzal, Zsuzsanna Bago-Horvath, Martin Filipits, Lidija Soelkner, Christian Fesl, Michael Gnant
Journal: Journal of Clinical Oncology (2024)

587 Background: MUC1 glycoprotein is overexpressed in over 90% of breast cancers. It is involved in oncogenesis and confers resistance to anti-cancer therapies, thus representing a promising therapeutic target. Tecemotide (liposomal BLP25; Stimuvax) is a MUC1-based therapeutic cancer vaccine. The aim of the prospective, multicenter randomized two-arm phase-II ABCSG 34 trial was to investigate the efficacy and safety of tecemotide in patients with early BC when given concomitantly with neoadjuvant Standard-of-Care (SoC) treatment. Methods: 400 patients with HER2- early BC were randomized 1:1 to receive preoperative SoC treatment with or without tecemotide: Postmenopausal women with luminal A tumors received 6 months of letrozole as SoC, while postmenopausal patients with TNBC, luminal B tumors, in whom chemotherapy was considered to be SoC, and all premenopausal patients received 4 x EC and 4 x Docetaxel q3w. Primary endpoint was Residual Cancer Burden (RCB0/I) at the time of surgery, long-term outcomes were measured as part of a translational project. Distant recurrence free survival (DRFS) and overall survival (OS) were analyzed with Cox regression models. Results: Long-term outcome data were available for 291 women of whom 236 had received chemotherapy as SoC: In these patients with evaluable RCB, the addition of tecemotide to neoadjuvant SoC was not associated with a significant increase in RCB0/I (36.4% versus 31.5%, p=0.42; 40.5% vs 34.8%, p=0.37 for the chemotherapy cohort). However, after a follow-up of 7 years, 80.8% of patients who had received SoC + tecemotide were alive and free from metastasis versus 64.7% who had received SoC alone (HR for DRFS: 0.53, 95% CI 0.34 - 0.83, p =0.005); 83.0% versus 68.2% were still alive (HR for OS 0.53, 95% CI 0.33-0.85, p =0.008). Women who had received chemotherapy + tecemotide had a particularly good outcome with a DRFS of 81.9% vs 65.0% (HR 0.50, 95% CI 0.31 – 0.83, p=0.007), and an OS of 83.6% vs 67.8% (HR 0.51, 95% CI 0.30 – 0.88, p=0.016). Conclusions: The MUC-1 vaccine tecemotide, when added to standard neoadjuvant systemic therapy, markedly improved DRFS and OS. Despite the exploratory nature of this observation, this is the first significant and profound long-term survival benefit of an anti-cancer vaccine in breast cancer patients reported to date. Additional studies are needed to understand in more detail the underlying mechanisms, and the optimal use of cancer vaccines in breast cancer treatment. Clinical trial information: 2011-004822-85 .
Standardization of gut microbiome analysis in sports
Authors: Laura Mancin, Antonio Paoli, Sara Berry, Javier T Gonzalez, Adam J Collins, Maria Antonia Lizarraga, Joao Felipe Mota, Segata Nicola, Ian Rollo
Journal: Cell Reports Medicine (2024)

The gut microbiome plays a significant role in physiological functions such as nutrient processing, vitamin production, inflammatory response, and immune modulation, which, in turn, are important contributors to athlete health and performance. To date, the interpretation, discussion, and visualization of microbiome results of athletes are challenging, due to a lack of standard parameters and reference data for collection and comparison. The purpose of this perspective piece is to provide researchers with an easy-to-understand framework for the collection, analysis, and data management related to the gut microbiome with a specific focus on athletic populations. In the absence of a consensus on microbiome research in the sports field, we hope that these considerations serve as foundational "best practice." Adherence to these standard operating procedures will accelerate the path toward improving the quality of data and ultimately our understanding of the influence of the gut microbiome in sport settings.
Toripalimab in combination with HBM4003, an anti-CTLA-4 heavy chain-only antibody, in advanced melanoma and other solid tumors: an open-label phase I trial
Authors: Bixia Tang, Yu Chen, Yu Jiang, Meiyu Fang, Quanli Gao, Xiubao Ren, Li Yao, Gang Huang, Jing Chen, Xiaoshi Zhang, Rongqing Li, Shuai Zhao, Meijuan Gao, Ruixuan Luo, Meng Qi, Feng Li, Fei Zheng, Michael Lee, Xiaolu Tao, Rong Duan, Jun Guo, Zhihong Chi, Chuanliang Cui
Journal: Journal for ImmunoTherapy of Cancer (2024)

HBM4003 is a novel anti-CTLA-4 heavy chain-only antibody, designed to enhance Treg ablation and antibody-dependent cell-mediated cytotoxicity while ensuring a manageable safety profile. This phase I trial investigated the safety, pharmacokinetics, immunogenicity and preliminary efficacy of HBM4003 plus with anti-PD-1 antibody toripalimab in patients with advanced solid tumors, especially focusing on melanoma.
PARP inhibitors enhance antitumor immune responses by triggering pyroptosis via TNF–caspase 8–GSDMD/E axis in ovarian cancer
Authors: Yu Xia, Pu Huang, Yi-Yu Qian, Zanhong Wang, Ning Jin, Xin Li, Wen Pan, Si-Yuan Wang, Ping Jin, Emmanuel Kwateng Drokow, Xiong Li, Qi Zhang, Zhengmao Zhang, Pingfei Li, Yong Fang, Xiang-Ping Yang, Zhiqiang Han, Qing-Lei Gao
Journal: Journal for ImmunoTherapy of Cancer (2024)

In addition to their established action of synthetic lethality in tumor cells, poly(ADP-ribose) polymerase inhibitors (PARPis) also orchestrate tumor immune microenvironment (TIME) that contributes to suppressing tumor growth. However, it remains not fully understood whether and how PARPis trigger tumor-targeting immune responses.
Evaluation of AI-assisted HER2 scoring in breast carcinoma-stained whole-slide images.
Authors: Florian Thomas, Bénédicte Cormier, Céline Bossard, Bruno Poulet, Emmanuelle Guinaudeau, Yahia Salhi, Ilham Chokri, Frédérique Jossic, Laëtitia Lambros, Isabelle De Pinieux, Soum Thanguturi, Jérôme Chetritt, Sanae Salhi
Journal: Journal of Clinical Oncology (2024)

e13029 Background: HER2 gene amplification occurs in 15% of invasive breast carcinomas. Given the exclusive effectiveness of HER2-targeted therapy in HER2-overexpressed/amplified carcinomas, accurate HER2 status assessment is crucial in clinical decision-making. Moreover, scores 1+ and 2+ not amplified have been shown to benefit from treatment with the new HER2-based antibody-drug conjugates. In this context, HER2 scoring needs to be highly accurate. We developed an artificial intelligence (AI) algorithm for precise, replicable quantification of HER2 protein overexpression, assisting pathologists in HER2 immunohistochemistry scoring. Methods: We developed a fully automated algorithm for assisting pathologists in HER2 scoring in breast carcinoma stained whole slides images (WSI). 5901mm2 of HER2 immunostained sections (standard protocol, with Roche Ultra, 4B5 Clone) of digitized (with several scanners) tumor tissue were annotated at magnification x5 by 10 senior pathologists and used to train a Deep Learning model for invasive region detection. Hence, 4793 square images (tiles) of size 256 pixels were annotated at the cell level, at magnification x40 and used to train another model. The proposed algorithm automatically detects invasive regions of the tumor and quantifies the tumor cells in these regions. It also characterizes each cell according to its membrane completeness and intensity and provides pathologists a readily interpretable score along with the details of the slide analysis (cells categories distribution and heatmap), in accordance with the 2018 ASCO/CAP guidelines. The proposed algorithm works in an end-to-end manner, without requiring any manual intervention from pathologists. Three breast expert pathologists scored an unseen dataset of 68 WSI. After a washout period of two months, they re-scored these WSI with AI assistance. The performances of the model are evaluated by comparing the inter-observer agreement rate with and without AI, and by comparing the model results with the pathologists ground truth. Results: The model demonstrated an overall balanced accuracy of 90.0% on the validation dataset. Moreover, the overall inter-observer agreement (Fleiss Kappa) significantly improved, going from 0.37 without A.I to 0.64 with AI assistance. Conclusions: The proposed fully automated solution could perform exhaustive tumor cell analysis in invasive tissue, without requiring any pathologist intervention. Moreover, such a solution could help to standardize the routine results between pathologists which can suffer from an important variability, thus improving the targeted therapeutic decision. Confusion matrix on the test set. True Label\Predicted Label 0 1+ 2+ 3+ 0 10 2 0 0 1+ 2 28 0 0 2+ 0 3 15 0 3+ 0 0 0 6
Synergistic effect of concurrent high molecular risk mutations and lower JAK2 mutant variant allele frequencies on prognosis in patients with myelofibrosis—insights from a multicenter study
Authors: Yu-Hung Wang, Chao-Hung Wei, Chien-Chin Lin, Carmelo Gurnari, Hussein Awada, Lina Benajiba, Rafael Daltro de Oliveira, Juliette Soret-Dulphy, Bruno Cassinat, Andrius Zucenka, Adrián Mosquera Orgueira, Chang-Tsu Yuan, Sze-Hwei Lee, Chi-Yuan Yao, Kristian Gurashi, Hsin-An Hou, Kiran Batta, Manuel Mateo Pérez Encinas, Wen-Chien Chou, Jaroslaw P Maciejewski, Daniel H Wiseman, Jean-Jacques Kiladjian, Hwei-Fang Tien
Journal: Leukemia (2024)
Gene therapy for diffuse pleural mesotheliomas in preclinical models by concurrent expression of NF2 and SuperHippo
Authors: Rui Zhu, Xincheng Liu, Xu Zhang, Zhenxing Zhong, Sixian Qi, Ruxin Jin, Yuan Gu, Yu Wang, Chen Ling, Kang Chen, Dan Ye, Fa-Xing Yu
Journal: Cell Reports Medicine (2024)
Clinical-proteomic classification and precision treatment strategy of chordoma
Authors: Huabin Yin, Jinbo Hu, Jianxuan Gao, Tong Su, Jiali Jin, Cong Jiang, Wenxuan Yin, Xiaowen Xu, Zhengyan Chang, Wei Sun, Zhengdong Cai, Wang Zhou, Ping Wang, Jun Lin, Dianwen Song, Tong Meng
Journal: Cell Reports Medicine (2024)
Neoadjuvant chemotherapy with FOLFOXIRI plus lateral lymph nodes dissection for the treatment of resectable rectal cancer with lateral lymph node metastasis: A single-arm, investigator-initiated, phase II trial.
Authors: Yongkun Sun, Yujuan Jiang, Haitao Zhou, Wei Pei, Zheng Jiang, Jianqiang Tang, Yan Song, Zhixun Zhao, Jichuan Quan, Mingguang Zhang, Xiyue Hu, BO CHEN, Aijiang Su, Yuan Tang, Erni Li, Qian Liu, Jun Jiang, Jianwei Liang, Xishan Wang
Journal: Journal of Clinical Oncology (2024)

3533 Background: There is a lack of standardization in the comprehensive treatment strategies for rectal cancer with lateral lymph node metastasis (LLNM), which results in an unfavorable oncological outcome. We conducted the present phase II trial by performing neoadjuvant chemotherapy with 5-fluorouracil, irinotecan, and oxaliplatin (FOLFOXIRI) regimen plus lateral lymph node dissection (LLND) for resectable rectal cancer with LLNM to decrease the lateral recurrence and distant metastasis rates. Methods: This prospective, single-arm phase II trial was conducted from April 2018 to February 2023, and included patients with cT3-4aN+M0 resectable rectal cancer and clinical suspicion of LLNM based on preoperative MRI. Patients were treated with three cycles of FOLFOXIRI, and those with evidence of treatment response continued to receive two cycles of FOLFOXIRI. Total mesorectal excision plus LLND was performed at 3-4 weeks after completing the last cycle of preoperative chemotherapy, followed by 3 cycles of XELOX. Results: A total of 58 patients engaged in this research, and 53 were finally enrolled. The pathological examination detected microscopic LLNM in 12 (22.6%) patients. The pathologic complete response (pCR) rate was 11.3% (6/53), and the downstaging (ypstage 0 to 1) rate was 30.2% (16/53). DFS events were observed in 7 patients, and OS events were reported in 2 patients after a median follow-up of 30 months. The 3-year DFS rate was 88.3%, the 3-year local recurrence-free survival rate was 94.7%, and the 3-year OS rate was 91.3%. There were 14 (26.4%) cases with six grade 3/4 adverse events. Conclusions: Neoadjuvant chemotherapy with the FOLFOXIRI regimen plus LLND can significantly reduce the risk of local recurrence and distant metastasis in resectable rectal cancer with LLNM, which may be a new treatment option. Clinical trial information: NCT04850027 . Variable, n (%) Total pCR (ypT0N0), n (%) 6 (11.3%) Total LNs harvested Median (IQR) 30 (24~40) LLNs harvested Median (IQR) 12 (8~17) Pathological T category ypTis 1 (1.9%) ypT0 6 (11.3%) ypT1 2 (3.8%) ypT2 11 (20.8%) ypT3 31 (58.5%) ypT4 2 (3.8%) Pathological N category ypN0 30 (56.6%) ypN1 15 (28.3%) ypN2 8 (15.1%) Pathological stage 0 6 (11.3%) I 10 (18.9%) II 17 (32.1%) III 20 (37.7%) Tumor regression grade* 0 1 (1.9%) 1 21 (39.6%) 2 12 (22.6%) 3 12 (22.6%) 4 5 (9.4%) Pathological LLN status Positive 12 (22.6%) Negative 41 (77.4%) Histologic grade Moderate 42 (79.2%) Poor/Mucinous/signet 11 (20.8%) Blood vessel invasion Yes 11 (20.8%) No 42 (79.2%) Perinervous invasion Yes 12 (22.6%) No 41 (77.4%)
A multi-institutional observer study of AI-aided oncologists' performance on treatment response assessment of bladder cancer.
Authors: Monika Joshi, Di Sun, Ajjai Shivaram Alva, Philip Palmbos, Yousef Zakharia, Rohan Garje, Heang-Ping Chan, Richard H. Cohan, Lubomir Hadjiiski
Journal: Journal of Clinical Oncology (2024)

4599 Background: Neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC) results in a complete response of 30-40%. The remaining patients who do not benefit from this approach are at risk for disease progression prior to RC. Prompt accurate treatment response assessment (TRA) of NAC prior to RC is crucial to guide treatment and minimize toxicity. Our study evaluated the impact of artificial intelligence (AI)-based decision support system (CDSS-T) on oncologists’ performance in identifying patients who respond completely (stage T0) to NAC. Methods: We conducted a multicenter retrospective-observational study. The pathological cancer stage after NAC f/u RC served as the reference standard. CT Urograms (CTU) of 123 patients were collected, with a total of 157 evaluable imaging pairs including pre- and post-NAC CTU (N of T0=40). Five oncologists from 3 institutions participated. We randomly selected 51 CTU pairs for each oncologist, and each one read the set of 51 cases twice with a washout period of 3 weeks to eliminate reading memory. Each reading session included sequential reading without and then with the aid of CDSS-T. The CDSS-T was developed by combining radiomics and deep-learning AI predictions. Inter-observer performance was analyzed by the ROC iMRMC method, and intra-observer performance measured by Krippendorff’s alpha (agreement: α) and Bland–Altman (variability: standard deviation (SD)) methods. Results: With CDSS-T aid, the 5 oncologists had a higher mean area under the curve (AUC) and smaller SD for both first readings (0.77±0.08 without, 0.86±0.07 with CDSS-T) and second readings (0.77±0.09 without, 0.84±0.04 with CDSS-T). With aid they also had higher intra-observer agreement (α: 0.70±0.05 without, 0.84±0.04 with CDSS-T) and smaller intra-observer variability (SD: 26.28±2.69 without, 19.75±2.86 with CDSS-T). Conclusions: CDSS-T improves oncologists’ accuracy in TRA, increases intra-observer agreement, and reduces intra-observer variability. A prospective study is ongoing in MIBC to validate the findings. Reading 1 (AUC) Reading 2 (AUC) Intra-observer agreement α Intra-observer variability SD Oncologists w/o CDSS-T w/ CDSS-T w/o CDSS-T w/ CDSS-T w/o CDSS-T w/ CDSS-T w/o CDSS-T w/ CDSS-T #1 0.65 0.75 0.73 0.78 0.69 0.83 30.46 21.57 #2 0.81 0.85 0.82 0.87 0.64 0.80 26.08 19.07 #3 0.81 0.89 0.77 0.83 0.73 0.85 26.05 18.67 #4 0.73 0.88 0.64 0.83 0.69 0.89 22.92 16.01 #5 0.86 0.93 0.87 0.87 0.77 0.80 25.91 23.45 Mean±SD 0.77±0.08 0.86±0.07 0.77±0.09 0.84±0.04 0.70±0.05 0.84±0.04 26.28±2.69 19.75±2.86
68Ga-DOTA-FAPI-46 PET/CT Imaging for Restaging in a Patient With Metastatic Pheochromocytoma
Authors: Rahime Şahin, Mehmet Can Baloğlu, Nurhan Ergül, Tevfik Fikret Çermik, Esra Arslan
Journal: Clinical Nuclear Medicine (2024)

Abstract Pheochromocytomas (PHEOs) are neural crest-derived tumors originating from the chromaffin cells of the adrenal medulla and were recognized as one of the subtypes of paragangliomas by the World Health Organization in 2022. 68 Ga-labeled somatostatin analog ( 68 Ga-DOTA-NOC, 68 Ga-DOTA-TOC, and 68 Ga-DOTA-TATE) PET imaging has shown significant performance compared with 123 MIBG scintigraphy in the diagnosis of paragangliomas. It is now known that fibroblast activation protein (FAP) is overexpressed by various cancer-associated fibroblasts, including PHEOs. We would like to present the findings of 68 Ga-DOTA-FAPI-46 PET/CT and 68 Ga-DOTA-TATE PET/CT imaging performed for restaging on a 42-year-old man diagnosed with metastatic PHEO.
A Challenging Case of Hyperfunctioning Submandibular Ectopic Thyroid Successfully Treated With 131I
Authors: Giusi Pisano, Serena Sassano, Esther Diana Rossi, Annamaria D'Amore, Luca Zagaria
Journal: Clinical Nuclear Medicine (2024)

Abstract Ectopic thyroid tissue is a rare condition, caused by aberrancy during thyroid gland embryogenesis. Any pathology involving the thyroid gland can also affect the ectopic tissue, including tumorigenesis. We report a challenging case of relapsed hyperthyroidism in a woman who already underwent subtotal thyroidectomy in 1995 and surgical revision in 2020 for multinodular toxic goiter. 99m Tc-pertechnetate scan revealed an area of radiotracer focal uptake at submandibular level, posing a differential diagnosis between salivary gland tumor and ectopic thyroid. Correlation with clinical history and ultimately histopathology led to diagnosis of hyperfunctioning submandibular ectopic tissue, successfully treating the patient with 131 I.