bluuebunny/crossref_metadata_2025 huggingface dataset:
Table S5 from Dual immune checkpoint blockade induces analogous alterations in the dysfunctional CD8+ T cell and activated Treg compartment
Authors: van der Leun Anne M. , Traets Joleen J.H. , Vos Joris L. , Elbers Joris B.W. , Patiwael Sanne , Qiao Xiaohang , Machuca-Ostos Mercedes , Thommen Daniela S. , Haanen John B.A.G. , Schumacher Ton N.M. , Zuur Charlotte L.
Published: September 2024

Differentially expressed genes between NK KLRC1 versus NK FGFBP2.
Table S1 from Dual immune checkpoint blockade induces analogous alterations in the dysfunctional CD8+ T cell and activated Treg compartment
Authors: van der Leun Anne M. , Traets Joleen J.H. , Vos Joris L. , Elbers Joris B.W. , Patiwael Sanne , Qiao Xiaohang , Machuca-Ostos Mercedes , Thommen Daniela S. , Haanen John B.A.G. , Schumacher Ton N.M. , Zuur Charlotte L.
Published: September 2024

Toxicity and primary tumor MPR rate of HNSCC cohorts in different studies.
Figure S3 from The origin of highly elevated cell-free DNA in healthy individuals and patients with pancreatic, colorectal, lung, or ovarian cancer
Authors: Mattox Austin K. , Douville Christopher , Wang Yuxuan , Popoli Maria , Ptak Janine , Silliman Natalie , Dobbyn Lisa , Schaefer Joy , Lu Steve , Pearlman Alexander H. , Cohen Joshua D. , Tie Jeanne , Gibbs Peter , Lahouel Kamel , Bettegowda Chetan , Hruban Ralph H. , Tomasetti Cristian , Jiang Peiyong , Chan K.C. Allen , Lo Yuk Ming Dennis , Papadopoulos Nickolas , Kinzler Kenneth W. , Vogelstein Bert
Published: September 2024

Supplemental Figure 3. Fraction of plasma cfDNA that could be attributed to high molecular weight genomic DNA in samples analyzed by RealSeqS.
Figure S1 from The origin of highly elevated cell-free DNA in healthy individuals and patients with pancreatic, colorectal, lung, or ovarian cancer
Authors: Mattox Austin K. , Douville Christopher , Wang Yuxuan , Popoli Maria , Ptak Janine , Silliman Natalie , Dobbyn Lisa , Schaefer Joy , Lu Steve , Pearlman Alexander H. , Cohen Joshua D. , Tie Jeanne , Gibbs Peter , Lahouel Kamel , Bettegowda Chetan , Hruban Ralph H. , Tomasetti Cristian , Jiang Peiyong , Chan K.C. Allen , Lo Yuk Ming Dennis , Papadopoulos Nickolas , Kinzler Kenneth W. , Vogelstein Bert
Published: September 2024

Supplemental Figure 1. Overview of the patient samples included in the present study.
Table S6 from Clinical efficacy of ONC201 in H3K27M-mutant diffuse midline gliomas is driven by disruption of integrated metabolic and epigenetic pathways
Authors: Venneti Sriram , Kawakibi Abed Rahman , Ji Sunjong , Waszak Sebastian M. , Sweha Stefan R. , Mota Mateus , Pun Matthew , Deogharkar Akash , Chung Chan , Tarapore Rohinton S. , Ramage Samuel , Chi Andrew , Wen Patrick Y. , Arrillaga-Romany Isabel , Batchelor Tracy T. , Butowski Nicholas A. , Sumrall Ashley , Shonka Nicole , Harrison Rebecca A. , de Groot John , Mehta Minesh , Hall Matthew D. , Daghistani Doured , Cloughesy Timothy F. , Ellingson Benjamin M. , Beccaria Kevin , Varlet Pascale , Kim Michelle M. , Umemura Yoshie , Garton Hugh , Franson Andrea , Schwartz Jonathan , Jain Rajan , Kachman Maureen , Baum Heidi , Burant Charles F. , Mottl Sophie L. , Cartaxo Rodrigo T. , John Vishal , Messinger Dana , Qin Tingting , Peterson Erik , Sajjakulnukit Peter , Ravi Karthik , Waugh Alyssa , Walling Dustin , Ding Yujie , Xia Ziyun , Schwendeman Anna , Hawes Debra , Yang Fusheng , Judkins Alexander R. , Wahl Daniel , Lyssiotis Costas A. , de la Nava Daniel , Alonso Marta M. , Eze Augustine , Spitzer Jasper , Schmidt Susanne V. , Duchatel Ryan J. , Dun Matthew D. , Cain Jason E. , Jiang Li , Stopka Sylwia A. , Baquer Gerard , Regan Michael S. , Filbin Mariella G. , Agar Nathalie Y.R. , Zhao Lili , Kumar-Sinha Chandan , Mody Rajen , Chinnaiyan Arul , Kurokawa Ryo , Pratt Drew , Yadav Viveka N. , Grill Jacques , Kline Cassie , Mueller Sabine , Resnick Adam , Nazarian Javad , Allen Joshua E. , Odia Yazmin , Gardner Sharon L. , Koschmann Carl
Published: September 2024

Radiographic response versus gene expression Spearman's correlation coefficient for all protein-coding genes.
Data from Late-stage metastatic melanoma emerges through a diversity of evolutionary pathways
Authors: Spain Lavinia , Coulton Alexander , Lobon Irene , Rowan Andrew , Schnidrig Desiree , Shepherd Scott T.C. , Shum Benjamin , Byrne Fiona , Goicoechea Maria , Piperni Elisa , Au Lewis , Edmonds Kim , Carlyle Eleanor , Hunter Nikki , Renn Alexandra , Messiou Christina , Hughes Peta , Nobbs Jaime , Foijer Floris , van den Bos Hilda , Wardenaar Rene , Spierings Diana C.J. , Spencer Charlotte , Schmitt Andreas M. , Tippu Zayd , Lingard Karla , Grostate Lauren , Peat Kema , Kelly Kayleigh , Sarker Sarah , Vaughan Sarah , Mangwende Mary , Terry Lauren , Kelly Denise , Biano Jennifer , Murra Aida , Korteweg Justine , Lewis Charlotte , OFlaherty Molly , Cattin Anne-Laure , Emmerich Max , Gerard Camille L. , Pallikonda Husayn Ahmed. , Lynch Joanna , Mason Robert , Rogiers Aljosja , Xu Hang , Huebner Ariana , McGranahan Nicholas , Al Bakir Maise , Murai Jun , Naceur-Lombardelli Cristina , Borg Elaine , Mitchison Miriam , Moore David A. , Falzon Mary , Proctor Ian , Stamp Gordon W H. , Nye Emma L. , Young Kate , Furness Andrew J.S. , Pickering Lisa , Stewart Ruby , Mahadeva Ula , Green Anna , Larkin James , Litchfield Kevin , Swanton Charles , Jamal-Hanjani Mariam , Turajlic Samra
Published: September 2024

Abstract
Understanding the evolutionary pathways to metastasis and resistance to immune checkpoint inhibitors (ICI) in melanoma is critical for improving outcomes. Here we present the most comprehensive intra-patient metastatic melanoma dataset assembled to date as part of the PEACE research autopsy programme, including 222 exome, 493 panel-sequenced, 161 RNA-seq, and 22 single-cell whole-genome sequencing samples from 14 ICI-treated patients. We observed frequent whole-genome doubling and widespread loss of heterozygosity, often involving antigen presentation machinery. We found KIT extrachromosomal DNA may have contributed to the lack of response to KIT inhibitors of a KIT-driven melanoma. At the lesion-level, MYC amplifications were enriched in ICI non-responders. Single-cell sequencing revealed polyclonal seeding of metastases originating from clones with different ploidy in one of the patients. Finally, we observed that brain metastases that diverged early in molecular evolution emerge late in disease. Overall, our study illustrates the diverse evolutionary landscape of advanced melanoma.
Data from Spatial Transcriptomics of Intraductal Papillary Mucinous Neoplasms of The Pancreas Identifies NKX6-2 as a Driver of Gastric Differentiation and Indolent Biological Potential
Authors: Sans Marta , Makino Yuki , Min Jimin , Rajapakshe Kimal I. , Yip-Schneider Michele , Schmidt C. Max , Hurd Mark W. , Burks Jared K. , Gomez Javier A. , Thege Fredrik I. , Fahrmann Johannes F. , Wolff Robert A. , Kim Michael P. , Guerrero Paola A. , Maitra Anirban
Published: September 2024

Abstract
Intraductal Papillary Mucinous Neoplasms (IPMNs) of the pancreas are bona fide precursor lesions of pancreatic ductal adenocarcinoma (PDAC). The most common subtype of IPMNs harbor a gastric foveolar-type epithelium, and these low-grade mucinous neoplasms are harbingers of IPMNs with high-grade dysplasia and cancer. The molecular underpinning of gastric differentiation in IPMNs is unknown, although identifying drivers of this indolent phenotype might enable opportunities for intercepting progression to high-grade IPMN and cancer. We conducted spatial transcriptomics on a cohort of IPMNs, followed by orthogonal and cross species validation studies, which established the transcription factor NKX6-2 as a key determinant of gastric cell identity in low-grade IPMNs. Loss of NKX6-2 expression is a consistent feature of IPMN progression, while re-expression of NKX6-2 in murine IPMN lines recapitulates the aforementioned gastric transcriptional program and glandular morphology. Our study identifies NKX6-2 as a previously unknown transcription factor driving indolent gastric differentiation in IPMN pathogenesis.
Supplementary tumor data for parameter fitting from Myeloid-derived suppressor–cell dynamics control outcomes in the metastatic niche
Authors: Kreger Jesse , Roussos Torres Evanthia T. , MacLean Adam L.
Published: September 2024

Ref: Spigel, et al. (2018). https://www.jto.org/article/S1556-0864(18)30603-8/ fulltext.
Supplementary Figures from Myeloid-derived suppressor–cell dynamics control outcomes in the metastatic niche
Authors: Kreger Jesse , Roussos Torres Evanthia T. , MacLean Adam L.
Published: September 2024

Supplementary Figures
Supplementary Data from Driver mutations dictate the immunological landscape and response to checkpoint immunotherapy of glioblastoma
Authors: Yeo Alan T. , Shah Rushil , Aliazis Konstantinos , Pal Rinku , Xu Tuoye , Zhang Piyan , Rawal Shruti , Rose Christopher M. , Varn Frederick S. , Appleman Vicky A. , Yoon Joon , Varma Hemant , Gygi Steven P. , Verhaak Roel G.W. , Boussiotis Vassiliki A. , Charest Al
Published: September 2024

supplementary figures & legends
Supplementary Data Table1 from Driver mutations dictate the immunological landscape and response to checkpoint immunotherapy of glioblastoma
Authors: Yeo Alan T. , Shah Rushil , Aliazis Konstantinos , Pal Rinku , Xu Tuoye , Zhang Piyan , Rawal Shruti , Rose Christopher M. , Varn Frederick S. , Appleman Vicky A. , Yoon Joon , Varma Hemant , Gygi Steven P. , Verhaak Roel G.W. , Boussiotis Vassiliki A. , Charest Al
Published: September 2024

Supplementary Table 1
Supplementary Tables from Influence of adipose tissue distribution, sarcopenia, and nutritional status on clinical outcomes after CD19 CAR T-cell therapy
Authors: Rejeski Kai , Cordas dos Santos David M. , Parker Nathan H. , Bücklein Veit L. , Winkelmann Michael , Jhaveri Khushali S. , Liu Lian , Trinkner Paul , Günther Sophie , Karschnia Philipp , Blumenberg Viktoria , Schmidt Christian , Kunz Wolfgang G. , von Bergwelt-Baildon Michael , Jain Michael D. , Theurich Sebastian , Subklewe Marion
Published: September 2024

Supplementary Tables
Supplementary Figure 5 from Regional variation in the tumor microenvironment, immune escape and prognostic factors in breast cancer in sub-Saharan Africa
Authors: Bauer Marcus , Vetter Martina , Stückrath Kathrin , Yohannes Meron , Desalegn Zelalem , Yalew Tewodros , Bekuretsion Yonas , Kenea Tariku W. , Joffe Maureen , Van Den Berg Eunice J. , Nikulu Julien Ilunga. , Bakarou Kamaté , Manraj Shyam S. , Ogunbiyi Olufemi J. , Ekanem Ima-Obong , Igbinoba Festus , Diomande Mohenou , Adebamowo Clement , Dzamalala Charles P. , Anele Angelica A. , Zietsman Annelle , Galukande Moses , Foerster Milena , dos-Santos-Silva Isabel , Liu Biying , Santos Pablo , Jemal Ahmedin , Abebe Tamrat , Wickenhauser Claudia , Seliger Barbara , McCormack Valerie , Kantelhardt Eva J.
Published: September 2024

Figure S5: MHC I expression in SSA
Supplementary Figure 4 from Regional variation in the tumor microenvironment, immune escape and prognostic factors in breast cancer in sub-Saharan Africa
Authors: Bauer Marcus , Vetter Martina , Stückrath Kathrin , Yohannes Meron , Desalegn Zelalem , Yalew Tewodros , Bekuretsion Yonas , Kenea Tariku W. , Joffe Maureen , Van Den Berg Eunice J. , Nikulu Julien Ilunga. , Bakarou Kamaté , Manraj Shyam S. , Ogunbiyi Olufemi J. , Ekanem Ima-Obong , Igbinoba Festus , Diomande Mohenou , Adebamowo Clement , Dzamalala Charles P. , Anele Angelica A. , Zietsman Annelle , Galukande Moses , Foerster Milena , dos-Santos-Silva Isabel , Liu Biying , Santos Pablo , Jemal Ahmedin , Abebe Tamrat , Wickenhauser Claudia , Seliger Barbara , McCormack Valerie , Kantelhardt Eva J.
Published: September 2024

Figure S4:PD-L1 expression and cytotoxicity
Supplemental Table 5 from mWTX-330, an IL 12 INDUKINE Molecule, Activates and Reshapes Tumor-infiltrating CD8+ T and NK Cells to Generate Antitumor Immunity
Authors: Nirschl Christopher J. , Brodkin Heather R. , Domonkos Celesztina , Dwyer Connor J. , Hicklin Daniel J. , Ismail Nesreen , Seidel-Dugan Cynthia , Steiner Philipp , Steuert Zoe , Sullivan Jenna M. , Winston William M. , Salmeron Andres
Published: September 2024

EC50 Values and Fold Change in Activity of WTX-330 in Primary Human Tblasts
Supplemental Table 3 from mWTX-330, an IL 12 INDUKINE Molecule, Activates and Reshapes Tumor-infiltrating CD8+ T and NK Cells to Generate Antitumor Immunity
Authors: Nirschl Christopher J. , Brodkin Heather R. , Domonkos Celesztina , Dwyer Connor J. , Hicklin Daniel J. , Ismail Nesreen , Seidel-Dugan Cynthia , Steiner Philipp , Steuert Zoe , Sullivan Jenna M. , Winston William M. , Salmeron Andres
Published: September 2024

Differential Gene Expression Analysis of EMT-6 Tumor Infiltrating CD8+ T cells
Supplementary Data from NL-201 upregulates MHC-I expression and intratumoral TCR diversity, and demonstrates robust antitumor activity as monotherapy and in combination with PD-1 blockade
Authors: Mortales Christie , Dutzar Benjamin , Chen Jerry , Chen Alex , Huard Justin , Walkey Carl , Swanson Ryan
Published: September 2024

Supplementary Table S1. Neo-2/15 maximum pSTAT5 signaling (maximal Mean fluorescent intensity, MFI) in human PBMCs and mouse splenocytes.
Supplementary Table S2. IL-2 Receptor Signaling in Primary Human and Cynomolgus Monkey CD8+ T Cells induced by IL-2, NL-201, and Neo2/15.
Supplementary Figure S1. A-B, Flow cytometric analysis of human PBMCs (A) and mouse splenocytes (B) for cell surface expression of IL-2Rα (CD25), IL-2Rβ (CD122), and IL-2Rγc (CD132).
Supplementary Figure S2. Flow cytometric analysis of CT26-hHER2 and CT26 cell death assessed by Annexin V labeling after a 6-hour co-culture with isolated Balb/c NK cells and indicated concentrations of IL-2R agonists.
Supplementary Figure S3. NL-201 demonstrates improved in vivo efficacy as compared to Neo-2/15.
Supplementary Figure S4. A-B, Flow cytometric analysis of MHC-I (A) and PD-L1 (B) surface expression on in vitro B16F10 cells cultured with the indicated concentrations of cytokines for 1 day.
Supplementary Figure S5. A-C, Tumor volume measurements of individual mice bearing subcutaneous B16F10 melanoma (A), EMT6 mammary carcinoma (B), and Renca renal adenocarcinoma (C) tumors.
Supplementary Figure S6. A-B, B16F10 tumor-bearing mice were given a single dose of NL-201 by intravenous administration and then harvested 5 days later for ex vivo flow cytometric analysis to measure the abundance of CD45+ cells (A) and CD3+ T cells of CD45+ gate (B).
Supplementary Fig. 5-7 from KRT17 promotes T-lymphocyte infiltration through the YTHDF2-CXCL10 axis in colorectal cancer
Authors: Liang Wenfeng , Liu Huashan , Zeng Ziwei , Liang Zhenxing , Xie Hao , Li Wenxin , Xiong Li , Liu Zhihang , Chen Mian , Jie Haiqing , Zheng Xiaobin , Huang Liang , Kang Liang
Published: September 2024

YTHDF2 expression is negatively correlated with CD3+ and CD8+ densities in tumor parenchyma and invasive margin in CRC.
Supplementary Fig. 1 from KRT17 promotes T-lymphocyte infiltration through the YTHDF2-CXCL10 axis in colorectal cancer
Authors: Liang Wenfeng , Liu Huashan , Zeng Ziwei , Liang Zhenxing , Xie Hao , Li Wenxin , Xiong Li , Liu Zhihang , Chen Mian , Jie Haiqing , Zheng Xiaobin , Huang Liang , Kang Liang
Published: September 2024

KRT17 is highly expressed in CRC tissues compared to tumor-adjacent tissue regardless of MMR status.
Supplementary Figure 11 from Feasibility and Safety of Personalized, Multi-Target, Adoptive Cell Therapy (IMA101): First-In-Human Clinical Trial in Patients with Advanced Metastatic Cancer
Authors: Tsimberidou Apostolia M. , Guenther Kerstin , Andersson Borje S. , Mendrzyk Regina , Alpert Amir , Wagner Claudia , Nowak Anna , Aslan Katrin , Satelli Arun , Richter Fabian , Kuttruff-Coqui Sabrina , Schoor Oliver , Fritsche Jens , Coughlin Zoe , Mohamed Ali S. , Sieger Kerry , Norris Becky , Ort Rita , Beck Jennifer , Vo Henry Hiep. , Hoffgaard Franziska , Ruh Manuel , Backert Linus , Wistuba Ignacio I. , Fuhrmann David , Ibrahim Nuhad K. , Morris Van Karlyle. , Kee Bryan K. , Halperin Daniel M. , Nogueras-González Graciela M. , Kebriaei Partow , Shpall Elizabeth J. , Vining David , Hwu Patrick , Singh-Jasuja Harpreet , Reinhardt Carsten , Britten Cedrik M. , Hilf Norbert , Weinschenk Toni , Maurer Dominik , Walter Steffen
Published: September 2024

Supplementary Figure 11
Supplemental Figure 6 from Feasibility and Safety of Personalized, Multi-Target, Adoptive Cell Therapy (IMA101): First-In-Human Clinical Trial in Patients with Advanced Metastatic Cancer
Authors: Tsimberidou Apostolia M. , Guenther Kerstin , Andersson Borje S. , Mendrzyk Regina , Alpert Amir , Wagner Claudia , Nowak Anna , Aslan Katrin , Satelli Arun , Richter Fabian , Kuttruff-Coqui Sabrina , Schoor Oliver , Fritsche Jens , Coughlin Zoe , Mohamed Ali S. , Sieger Kerry , Norris Becky , Ort Rita , Beck Jennifer , Vo Henry Hiep. , Hoffgaard Franziska , Ruh Manuel , Backert Linus , Wistuba Ignacio I. , Fuhrmann David , Ibrahim Nuhad K. , Morris Van Karlyle. , Kee Bryan K. , Halperin Daniel M. , Nogueras-González Graciela M. , Kebriaei Partow , Shpall Elizabeth J. , Vining David , Hwu Patrick , Singh-Jasuja Harpreet , Reinhardt Carsten , Britten Cedrik M. , Hilf Norbert , Weinschenk Toni , Maurer Dominik , Walter Steffen
Published: September 2024

Supplemental Figure 6
Supplemental Figure 4 from Feasibility and Safety of Personalized, Multi-Target, Adoptive Cell Therapy (IMA101): First-In-Human Clinical Trial in Patients with Advanced Metastatic Cancer
Authors: Tsimberidou Apostolia M. , Guenther Kerstin , Andersson Borje S. , Mendrzyk Regina , Alpert Amir , Wagner Claudia , Nowak Anna , Aslan Katrin , Satelli Arun , Richter Fabian , Kuttruff-Coqui Sabrina , Schoor Oliver , Fritsche Jens , Coughlin Zoe , Mohamed Ali S. , Sieger Kerry , Norris Becky , Ort Rita , Beck Jennifer , Vo Henry Hiep. , Hoffgaard Franziska , Ruh Manuel , Backert Linus , Wistuba Ignacio I. , Fuhrmann David , Ibrahim Nuhad K. , Morris Van Karlyle. , Kee Bryan K. , Halperin Daniel M. , Nogueras-González Graciela M. , Kebriaei Partow , Shpall Elizabeth J. , Vining David , Hwu Patrick , Singh-Jasuja Harpreet , Reinhardt Carsten , Britten Cedrik M. , Hilf Norbert , Weinschenk Toni , Maurer Dominik , Walter Steffen
Published: September 2024

Supplemental Figure 4
Supplemental Figure 2 from Feasibility and Safety of Personalized, Multi-Target, Adoptive Cell Therapy (IMA101): First-In-Human Clinical Trial in Patients with Advanced Metastatic Cancer
Authors: Tsimberidou Apostolia M. , Guenther Kerstin , Andersson Borje S. , Mendrzyk Regina , Alpert Amir , Wagner Claudia , Nowak Anna , Aslan Katrin , Satelli Arun , Richter Fabian , Kuttruff-Coqui Sabrina , Schoor Oliver , Fritsche Jens , Coughlin Zoe , Mohamed Ali S. , Sieger Kerry , Norris Becky , Ort Rita , Beck Jennifer , Vo Henry Hiep. , Hoffgaard Franziska , Ruh Manuel , Backert Linus , Wistuba Ignacio I. , Fuhrmann David , Ibrahim Nuhad K. , Morris Van Karlyle. , Kee Bryan K. , Halperin Daniel M. , Nogueras-González Graciela M. , Kebriaei Partow , Shpall Elizabeth J. , Vining David , Hwu Patrick , Singh-Jasuja Harpreet , Reinhardt Carsten , Britten Cedrik M. , Hilf Norbert , Weinschenk Toni , Maurer Dominik , Walter Steffen
Published: September 2024

Supplemental Figure 2
Supplementary Figures from Immunogenetic metabolomics reveals key enzymes that modulate CAR T-cell metabolism and function
Authors: Renauer Paul , Park Jonathan J. , Bai Meizhu , Acosta Arianny , Lee Won-Ho , Lin Guang Han , Zhang Yueqi , Dai Xiaoyun , Wang Guangchuan , Errami Youssef , Wu Terence , Clark Paul , Ye Lupeng , Yang Quanjun , Chen Sidi
Published: September 2024

Supplementary Figures 1-10
Supplementary Figure 4 from Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Influence on Soluble and Membrane Bound ICOS in Combination with Immune Checkpoint Blockade
Authors: Li Xiaoyu , Li Jingjing , zheng Yue , Lee Sandra J. , Zhou Jun , Giobbie-Hurder Anita , Butterfield Lisa H. , Dranoff Glenn , Hodi F. Stephen.
Published: September 2024

Supplementary figure 4
Supplementary Figures from Aerobic exercise alters the melanoma microenvironment and modulates ERK5 S496 phosphorylation
Authors: Savage Hannah , Pareek Sumedha , Lee Jonghae , Ballarò Riccardo , Conterno Minussi Darlan , Hayek Karma , Sadullozoda Mumina , Lochmann Brooke S. , McQuade Jennifer L. , LaVoy Emily C. , Marmonti Enrica , Patel Hetal , Wang Guangyu , Imanishi Masaki , Kotla Sivareddy , Abe Jun-ichi , Schadler Keri L.
Published: September 2024

Supplementary Figures S1-S8
Supplementary Figures S1-S13 from Tumor-targeted non-ablative radiation promotes solid tumor CAR T-cell therapy efficacy
Authors: Quach Hue Tu. , Skovgard Matthew S. , Villena-Vargas Jonathan , Bellis Rebecca Y. , Chintala Navin K. , Amador-Molina Alfredo , Bai Yang , Banerjee Srijita , Saini Jasmeen , Xiong Yuquan , Vista William-Ray , Byun Alexander J. , De Biasi Andreas , Zeltsman Masha , Mayor Marissa , Morello Aurore , Mittal Vivek , Gomez Daniel R. , Rimner Andreas , Jones David R. , Adusumilli Prasad S.
Published: September 2024

Supplementary Figures 1-13 with associated legends
Supplementary Data from Ncoa2 promotes CD8+ T cell-mediated anti-tumor immunity by stimulating T-cell activation via upregulation of PGC-1α critical for mitochondrial function
Authors: Zhong Xiancai , Wu Hongmin , Ouyang Ching , Zhang Wencan , Shi Yun , Wang Yi-Chang , Ann David K. , Gwack Yousang , Shang Weirong , Sun Zuoming
Published: September 2024

All supplementray figures and tables
Data from Myeloid-derived suppressor–cell dynamics control outcomes in the metastatic niche
Authors: Kreger Jesse , Roussos Torres Evanthia T. , MacLean Adam L.
Published: September 2024

Abstract
Myeloid-derived suppressor cells (MDSCs) play a prominent role in the tumor microenvironment. A quantitative understanding of the tumor–MDSC interactions that influence disease progression is critical, and currently lacking. We developed a mathematical model of metastatic growth and progression in immune-rich tumor microenvironments. We modeled the tumor–immune dynamics with stochastic delay differential equations and studied the impact of delays in MDSC activation/recruitment on tumor growth outcomes. In the lung environment, when the circulating level of MDSCs was low, the MDSC delay had a pronounced impact on the probability of new metastatic establishment: blocking MDSC recruitment could reduce the probability of metastasis by as much as 50%. To predict patient-specific MDSC responses we fit to the model individual tumors treated with immune checkpoint inhibitors via Bayesian parameter inference. We reveal that control of the inhibition rate of natural killer (NK) cells by MDSCs had a larger influence on tumor outcomes than controlling the tumor growth rate directly. Posterior classification of tumor outcomes demonstrates that incorporating knowledge of the MDSC responses improved predictive accuracy from 63% to 82%. Investigation of the MDSC dynamics in an environment low in NK cells and abundant in cytotoxic T cells revealed, in contrast, that small MDSC delays no longer impacted metastatic growth dynamics. Our results illustrate the importance of MDSC dynamics in the tumor microenvironment overall and predict interventions promoting shifts toward less immune-suppressed states. We propose that there is a pressing need to consider MDSCs more often in analyses of tumor microenvironments.
Data from MYC induces immunotherapy and interferon-γ resistance through downregulation of JAK2
Authors: Markovits Ettai , Harush Ortal , Baruch Erez N. , Shulman Eldad D. , Debby Assaf , Itzhaki Orit , Anafi Liat , Danilevsky Artem , Shomron Noam , Ben-Betzalel Guy , Asher Nethanel , Shapira-Frommer Ronnie , Schachter Jacob , Barshack Iris , Geiger Tamar , Elkon Ran , Besser Michal J. , Markel Gal
Published: September 2024

Abstract
Immunotherapy has revolutionized the treatment of advanced melanoma. Because the pathways mediating resistance to immunotherapy are largely unknown, we conducted transcriptome profiling of pre-immunotherapy tumor biopsies from melanoma patients that received PD-1 blockade or adoptive cell therapy with tumor-infiltrating lymphocytes. We identified two melanoma-intrinsic, mutually exclusive gene programs, which were controlled by interferon-γ (IFNγ) and MYC, and the association with immunotherapy outcome. MYC-overexpressing melanoma cells exhibited lower IFNγ responsiveness, which was linked with JAK2 downregulation. Luciferase activity assays, under the control of JAK2 promoter, demonstrated reduced activity in MYC-overexpressing cells, which was partly reversible upon mutagenesis of a MYC E-box binding site in the JAK2 promoter. Moreover, silencing of MYC or its co-factor MAX with siRNA increased JAK2 expression and IFNγ responsiveness of melanomas, while concomitantly enhancing the effector functions of T cells co-incubated with MYC-overexpressing cells. Thus, we propose that MYC plays a pivotal role in immunotherapy resistance through downregulation of JAK2.
Data from mWTX-330, an IL 12 INDUKINE Molecule, Activates and Reshapes Tumor-infiltrating CD8+ T and NK Cells to Generate Antitumor Immunity
Authors: Nirschl Christopher J. , Brodkin Heather R. , Domonkos Celesztina , Dwyer Connor J. , Hicklin Daniel J. , Ismail Nesreen , Seidel-Dugan Cynthia , Steiner Philipp , Steuert Zoe , Sullivan Jenna M. , Winston William M. , Salmeron Andres
Published: September 2024

Abstract
IL-12 is a pleotropic inflammatory cytokine that has broad stimulatory effects on various immune cell populations, making it an attractive target for cancer immunotherapy. However, despite generating robust antitumor activity in syngeneic murine tumor models, clinical administration of IL-12 has been limited by severe toxicity. mWTX-330 is a selectively inducible INDUKINE molecule comprised of a half-life extension domain and an inactivation domain linked to chimeric IL-12 by tumor protease–sensitive linkers. Systemic administration of mWTX-330 in mice was well tolerated, resulted in robust antitumor immunity in multiple tumor models, and preferentially activated tumor-infiltrating immune cells rather than immune cells present in peripheral tissues. Antitumor activity was dependent on in vivo processing of the protease cleavable linkers and required CD8+ T cells for full efficacy. Within the tumor, mWTX-330 increased the frequency of cross-presenting dendritic cells (DCs), activated natural killer (NK) cells, skewed conventional CD4+ T cells toward a T helper 1 (TH1) phenotype, drove regulatory T cells (Treg) fragility, and increased the frequency of polyfunctional CD8+ T cells. mWTX-330 treatment also increased the clonality of tumor-infiltrating T cells by expanding underrepresented T-cell receptor (TCR) clones, drove CD8+ T and NK cells towards increased mitochondrial respiration and fitness, and decreased the frequency of TOX+ exhausted CD8+ T cells within the tumor. A fully human version of this INDUKINE molecule was stable in human serum, was reliably and selectively processed by human tumor samples, and is currently in clinical development.
 
Data from A bispecific γδ T-cell engager targeting EGFR activates a potent Vγ9Vδ2 T cell–mediated immune response against EGFR-expressing tumors
Authors: King Lisa A. , Toffoli Elisa C. , Veth Myrthe , Iglesias-Guimarais Victoria , Slot Manon C. , Amsen Derk , van de Ven Rieneke , Derks Sarah , Fransen Marieke F. , Tuynman Jurriaan B. , Riedl Thilo , Roovers Rob C. , Adang Anton E.P. , Ruben Jurjen M. , Parren Paul W.H.I. , de Gruijl Tanja D. , van der Vliet Hans J.
Published: September 2024

Abstract
Vγ9Vδ2 T cells are effector cells with proven antitumor efficacy against a broad range of cancers. This study aimed to assess the antitumor activity and safety of a bispecific antibody directing Vγ9Vδ2 T cells to EGFR-expressing tumors. An EGFR-Vδ2 bispecific T-cell engager (bsTCE) was generated and its capacity to activate Vγ9Vδ2 T cells and trigger antitumor activity were tested in multiple in vitro, in vivo, and ex vivo models. Studies to explore safety were conducted using cross-reactive surrogate engagers in non-human primates (NHP). We found that Vγ9Vδ2 T cells from peripheral blood and tumor specimens of patients with EGFR+ cancers had a distinct immune checkpoint expression profile characterized by low levels of PD-1, LAG-3, and TIM-3. Vγ9Vδ2 T cells could be activated by EGFR-Vδ2 bsTCEs to mediate lysis of various EGFR+ patient-derived tumor samples and substantial tumor growth inhibition and improved survival were observed in in vivo xenograft mouse models using PBMCs as effector cells. EGFR-Vδ2 bsTCEs exerted preferential activity towards EGFR+ tumor cells and induced downstream activation of CD4+ and CD8+ T cells and NK cells without concomitant activation of suppressive regulatory T cells observed with EGFR-CD3 bsTCEs. Administration of fully cross-reactive and half-life extended surrogate engagers to NHPs did not trigger signals in the safety parameters that were assessed. Considering the effector and immune-activating properties of Vγ9Vδ2 T cells, the preclinical efficacy data and acceptable safety profile reported here provide a solid basis for testing EGFR-Vδ2 bsTCEs in patients with EGFR+ malignancies.
Data from Tumor-targeted non-ablative radiation promotes solid tumor CAR T-cell therapy efficacy
Authors: Quach Hue Tu. , Skovgard Matthew S. , Villena-Vargas Jonathan , Bellis Rebecca Y. , Chintala Navin K. , Amador-Molina Alfredo , Bai Yang , Banerjee Srijita , Saini Jasmeen , Xiong Yuquan , Vista William-Ray , Byun Alexander J. , De Biasi Andreas , Zeltsman Masha , Mayor Marissa , Morello Aurore , Mittal Vivek , Gomez Daniel R. , Rimner Andreas , Jones David R. , Adusumilli Prasad S.
Published: September 2024

Abstract
Infiltration of tumor by T cells is a prerequisite for successful immunotherapy of solid tumors. In this study, we investigate the influence of tumor-targeted radiation on chimeric antigen receptor (CAR) T-cell therapy tumor infiltration, accumulation, and efficacy in clinically relevant models of pleural mesothelioma and non-small cell lung cancers. We use a non-ablative dose of tumor-targeted radiation prior to systemic administration of mesothelin-targeted CAR T cells to assess infiltration, proliferation, anti-tumor efficacy, and functional persistence of CAR T cells at primary and distant sites of tumor. A tumor-targeted, non-ablative dose of radiation promotes early and high infiltration, proliferation, and functional persistence of CAR T cells. Tumor-targeted radiation promotes tumor-chemokine expression and chemokine-receptor expression in infiltrating T cells, and results in a subpopulation of higher-intensity CAR-expressing T cells with high co-expression of chemokine receptors that further infiltrate distant sites of disease, enhancing CAR T-cell anti-tumor efficacy. Enhanced CAR T-cell efficacy is evident in models of both high-mesothelin-expressing mesothelioma and mixed-mesothelin-expressing lung cancer—two thoracic cancers for which radiation therapy is part of the standard of care. Our results strongly suggest that the use of tumor-targeted radiation prior to systemic administration of CAR T cells may substantially improve CAR T-cell therapy efficacy for solid tumors. Building on our observations, we describe a translational strategy of “sandwich” cell therapy for solid tumors that combines sequential metastatic site–targeted radiation and CAR T cells—a regional solution to overcome barriers to systemic delivery of CAR T cells.
Data from Tumor cell–intrinsic c-Myb upregulation stimulates antitumor immunity in a murine colorectal cancer model
Authors: van Gogh Merel , Glaus Garzon Jesus F. , Sahin Dilara , Knopfova Lucia , Benes Petr , Boyman Onur , Jurisica Igor , Borsig Lubor
Published: September 2024

Abstract
The transcription factor c-Myb is overexpressed in many different types of solid tumors, including colorectal cancer. However, its exact role in tumorigenesis is unclear. In this study, we show that tumor-intrinsic c-Myb expression in mouse models of colon cancer and melanoma suppresses tumor growth. While no differences in proliferation, apoptosis, and angiogenesis of tumors were evident tumors with distinct levels of c-Myb expression, we observed changes in intratumoral immune cell infiltrates. MC38 tumors with upregulated c-Myb expression showed increased numbers of CD103+ dendritic cells and eosinophils, but decreased tumor-associated macrophages (TAMs). Concomitantly, an increase in the number of activated cytotoxic CD8+ T cells upon c-Myb upregulation was observed, which correlated with a pro-inflammatory tumor microenvironment and increased numbers of M1 polarized TAMs. Mechanistically, c-Myb upregulation in immunogenic MC38 colon cancer cells resulted in enhanced expression of immunomodulatory genes, including those encoding 2-microglobulin and IFNβ, and decreased expression of the gene encoding the chemokine receptor CCR2. The increased numbers of activated cytotoxic CD8+ T cells contributed to tumor growth attenuation. In poorly immunogenic CT26, LLC, and B16-BL6 tumor cells, c-Myb upregulation did not affect the immunomodulatory gene expression. Despite this, c-Myb upregulation led to reduced B16-BL6 tumor growth but it did not affect tumor growth of CT26 and LLC tumors. Altogether, we postulate that c-Myb functions as a tumor suppressor in a tumor cell–type specific manner and modulates antitumor immunity.
Data from Glioblastoma vascular plasticity limits effector T-cell infiltration and is blocked by cAMP activation
Authors: Qin Zixi , Huang Youwei , Li Zeying , Pan Guopeng , Zheng Liangying , Xiao Xiao , Wang Fang , Chen Jiahong , Chen Xueqin , Lin Xi , Li Kai , Yan Guangmei , Zhang Haipeng , Xing Fan
Published: September 2024

Abstract
Glioblastoma (GBM) is the deadliest form of brain cancer, characterized as a highly angiogenetic and immunosuppressive malignancy. Although immune checkpoint blockades have revolutionized cancer therapy, their therapeutic efficacy in GBM has been far less than expected or even ineffective. Here, we reveal that the genomic signature of glioma-derived endothelial cells (GdECs) correlates with an immunosuppressive state and poor prognosis of glioma patients. In vitro model of GdECs differentiation is established for drug screening, and we identify that cAMP activators could effectively block the GdECs formation by inducing oxidative stress. cAMP activator impairs the GdECs differentiation in vivo, normalizes the tumor vessels, and alters the immune profile, especially increasing the influx and function of CD8+ effector T cells. The dual blockade of GdECs and PD-1 induces tumor regression and establishes anti-tumor immune memory. Our study reveals that endothelial transdifferentiation of GBM shapes an endothelial immune cell barrier and supports the clinical development of combining GdECs blockade and immunotherapy for GBM.
Data from ANXA1 promotes tumor immune evasion by binding PARP1 and upregulating Stat3-induced expression of PD-L1 in multiple cancers
Authors: Xiao Ding , Zeng Ting , Zhu Wei , Yu Zheng-Zheng , Huang Wei , Yi Hong , Lu Shan-Shan , Feng Juan , Feng Xue-Ping , Wu Di , Wen Qi , Zhou Jian-Hua , Yuan Li , Zhuang Wei , Xiao Zhi-Qiang
Published: September 2024

Abstract
The deregulation of annexin A1 (ANXA1), a regulator of inflammation and immunity, leads to cancer growth and metastasis. However, whether ANXA1 is involved in cancer immunosuppression is still unclear. Here, we report that ANXA1 knockdown (i) dramatically downregulates programmed cell death-ligand 1 (PD-L1) expression in breast cancer, lung cancer, and melanoma cells; (ii) promotes T cell-mediated killing of cancer cells in vitro; and (iii) inhibits cancer immune escape in immune-competent mice via downregulating PD-L1 expression and increasing the number and killing activity of CD8+ T cells. Mechanistically, ANXA1 functioned as a sponge molecule for interaction of PARP1 and Stat3. Specifically, binding of ANXA1 to PARP1 decreased PARP1’s binding to Stat3, which reduced poly(ADP-ribosyl)ation and dephosphorylation of Stat3 and thus, increased Stat3’s transcriptional activity, leading to transcriptionally upregulated expression of PD-L1 in multiple cancer cells. In clinical samples, expression of ANXA1 and PD-L1 was significantly higher in breast cancer, non-small cell lung cancer, and skin cutaneous melanoma compared to corresponding normal tissues and positively correlated in cancer tissues. Moreover, using both ANXA1 and PD-L1 proteins for predicting efficacy of anti-PD-1 immunotherapy and patient prognosis were superior to using individual proteins. Our data suggest that ANXA1 promotes cancer immune escape via binding PARP1 and upregulating Stat3-induced expression of PD-L1, that ANXA1 is a potential new target for cancer immunotherapy, and combination of ANXA1 and PD-L1 expression is a potential marker for predicting efficacy of anti-PD-1 immunotherapy in multiple cancers.
Supplementary Table S6 from In vivo screening unveils pervasive RNA-binding protein dependencies in leukemic stem cells and identifies ELAVL1 as a therapeutic target
Authors: Vujovic Ana , de Rooij Laura , Keyvani Chahi Ava , Chen He Tian , Yee Brian A. , Loganathan Sampath K. , Liu Lina , Chan Derek C. H. , Tajik Amanda , Tsao Emily , Moreira Steven , Joshi Pratik , Xu Joshua , Wong Nicholas , Balde Zaldy , Jahangiri Soheil , Zandi Sasan , Aigner Stefan , Dick John E. , Minden Mark D. , Schramek Daniel , Yeo Gene W. , Hope Kristin J.
Published: September 2024

Table S6 shows altered gene sets identified by GSEA of the ELAVL1 knockout RN2c RNA-sequencing data set.
Supplementary Table S3 from In vivo screening unveils pervasive RNA-binding protein dependencies in leukemic stem cells and identifies ELAVL1 as a therapeutic target
Authors: Vujovic Ana , de Rooij Laura , Keyvani Chahi Ava , Chen He Tian , Yee Brian A. , Loganathan Sampath K. , Liu Lina , Chan Derek C. H. , Tajik Amanda , Tsao Emily , Moreira Steven , Joshi Pratik , Xu Joshua , Wong Nicholas , Balde Zaldy , Jahangiri Soheil , Zandi Sasan , Aigner Stefan , Dick John E. , Minden Mark D. , Schramek Daniel , Yeo Gene W. , Hope Kristin J.
Published: September 2024

Table S3 shows clinical information for all AML patient specimens used in this study.
Table S4 from A SINGLE-CELL TAXONOMY PREDICTS INFLAMMATORY NICHE REMODELING TO DRIVE TISSUE FAILURE AND OUTCOME IN HUMAN AML
Authors: Chen Lanpeng , Pronk Eline , van Dijk Claire , Bian Yujie , Feyen Jacqueline , van Tienhoven Tim , Yildirim Meltem , Pisterzi Paola , De Jong Madelon M E. , Bastidas Alejandro , Hoogenboezem Remco M. , Wevers Chiel , Bindels Eric M. , Löwenberg Bob , Cupedo Tom , Sanders Mathijs A. , Raaijmakers Marc HGP.
Published: September 2024

Table S4 Differentially expressed genes and transcriptional programs (GSEA Hallmark) in BMSCs from AML vs. BMSCs from NBM (scRNAseq)
Figure S1 from Synergistic Effects of PARP Inhibition and Cholesterol Biosynthesis Pathway Modulation
Authors: Rutkowska Anna , Eberl H. Christian , Werner Thilo , Hennrich Marco L. , Sévin Daniel C. , Petretich Massimo , Reddington James P. , Pocha Shirin , Gade Stephan , Martinez-Segura Amalia , Dvornikov Dmytro , Karpiak Joel , Sweetman Gavain M.A. , Fufezan Christian , Duempelfeld Birgit , Braun Florian , Schofield Christopher , Keles Hakan , Alvarado David , Wang Zhuo , Jansson Keith H. , Faelth-Savitski Maria , Curry Edward , Remlinger Katja , Stronach Euan A. , Feng Bin , Sharma Geeta , Coleman Kevin , Grandi Paola , Bantscheff Marcus , Bergamini Giovanna
Published: September 2024

Selectivity profiling and Niraparib-LSS interaction
High-Risk Cannabis Use: A Proposal of an Operational Definition through Delphi Methodology for Scientific Consensus
Authors: Oliveras Clara , Guzman Cortez Pablo Rodrigo , Nuno Laura , Colom Joan , Casajuana Kögel Cristina , Pascual Francisco , Fernández-Artamendi Sergio , Gual Antoni , Balcells-Oliveró Mercè , López-Pelayo Hugo
Published: September 2024

Introduction: Cannabis ranks as one of the most widely used psychoactive substances worldwide. Its usage has been reported as a risk factor for developing a variety of physical and mental health issues, alongside social and economic problems. According to the World Health Organization (WHO), hazardous (or high-risk) substance use is defined as “a pattern of substance use that increases the risk of harmful consequences for the user.” The primary objective of this study was to achieve a consensus on an operational definition of high-risk cannabis use suitable for a European jurisdiction (Spain). Methods: A three round Delphi study was conducted. The Delphi technique entails group decision-making and iterative forecasting by consulting a panel of experts and conducting systematic feedback rounds. An online survey was distributed among a diverse expert panel comprising professionals from Spain working on fields related to cannabis use (research, policy planning, and clinical professionals). One-hundred ninety-nine invitations were sent to experts, of which forty-five (22.6%) accepted to participate. All participants were provided the option to revise a background document with the latest compiled scientific evidence and guidelines related to health and social conditions associated to cannabis usage. This background document also proposed the quantification of dose using a standardized unit established for the population of Spain (the Standard Joint Unit or SJU) based on quantity of cannabis main psychoactive constituent, 9-tetrahydrocannabinol (9-THC) (1 SJU = 1 joint = 0.25 g of cannabis = 7 mg of 9-THC). Three rounds of Likert scale and open-ended questions were administered until consensus, defined as ≥75% agreement, was attained. Results: Consensus was reached on defining high-risk cannabis use as the usage of more than 4 SJU (>28 mg THC) per week or any use of cannabis with potency >10% THC. Concurrent use of cannabis with other drugs was also considered high risk, while the smoked route was considered the riskiest administration route. It was also agreed that vulnerable groups for high-risk cannabis use (for whom any pattern of cannabis use represents high risk of harm) include individuals under the age of 21, pregnant or breastfeeding women, individuals with psychiatric history, those with medical health issues related to cannabis use, professional drivers and heavy machine operators. Conclusion: This operational definition of high-risk cannabis use for Spain elucidates usage patterns and individual vulnerability factors predictive of heightened harm. Its adoption holds potential to inform decision-making among individuals, professionals, and policy-makers, facilitating evidence-based interventions aimed at prevention and risk reduction.
Use of Cannabidiol-Dominant Extract as Co-Adjuvant Therapy for Type 2 Diabetes Mellitus Treatment in Feline: Case Report
Authors: Massabo José Ignacio , Puiatti Gabriela , Ferrero Paola
Published: September 2024

Introduction: Diabetes mellitus (DM) is a common endocrinopathy in felines. Treatment is based on glycemic control and management of clinical signs by insulin administration coupled with a low-carbohydrate and high-protein content diet. However, achieving adequate remission or glycemia control is not always possible. Effects of cannabinoids on the regulation of glucose uptake and the incidence of diabetes have been observed in experimental models. Nevertheless, little is known about their possible relevance in controlling this condition in veterinary and human medicine. Case Presentation: This is a case study of an 18-year-old, neutered, mixed-breed female domestic longhair cat diagnosed with type 2 DM. She was treated with long-acting glargine (3–5 IU/12 h), and her diet changed to ultra-processed commercial food for diabetic cats. Three months after the start of the treatment with insulin, cannabidiol (CBD)-enriched extract in handmade olive oil, tetrahydrocannabinol: CBD ratio = 1:24, was incorporated. The route of administration was oromucosal. After 3 months, the glycemia was reduced. The patient decreased the polyuria/polydipsia, recovered sleep cycles, remained attentive to all movements, and increased her physical activity. Conclusion: This report provides evidence that using a CBD-rich extract was effective as a co-adjuvant in alleviating clinical signs of DM and concurrent disorders, allowing for the reduction of insulin intake.
Dose-Dependent Relationship between Iron Metabolism and Perioperative Myocardial Injury in Cardiac Surgery with Cardiopulmonary Bypass: A Retrospective Analysis
Authors: Li Qian , Lv Hong , Chen Yuye , Shen Jingjia , Shi Jia , Zhou Chenghui
Published: September 2024

Introduction: We sought to comprehensively explore the potential linear and nonlinear relationship between preoperative iron metabolism and perioperative myocardial injury (PMI) following cardiac surgery with cardiopulmonary bypass (CPB). Methods: Patients who underwent cardiac surgery with CPB between December 2018 and April 2021 were retrospectively collected. The measurements of iron metabolism included serum iron (SI), serum ferritin (SF), transferrin (TRF), transferrin saturation (TS), and total iron-binding capacity (TIBC). Logistic regression and restricted cubic spline (RCS) models were used for linear and nonlinear analysis. The primary outcome was PMI with a 100× upper reference limit. Results: Of 2,420 patients screened, 744 eligible patients were enrolled for the final analysis. The incidence of PMI was 25.7%. No significant linear relationship was observed. In the RCS models adjusted with age (median: 56), female, and history of diabetes, a statistically significant difference was detected between TRF (p for nonlinear 0.0152) or TIBC (p for nonlinear 0.0477) and PMI. The gentle U-shaped relationship observed between TRF, TIBC, and PMI suggests that when TRF and TIBC increase, the risk decreases, reaching its lowest point when TRF = 2.4 and TIBC = 54. Nevertheless, as TRF and TIBC continue to increase, the risk starts to rise again. Subgroup analyses yielded consistent findings, with a notable emphasis on older patients who were more susceptible to variations in iron metabolism. Conclusion: Iron metabolism, including TRF, and TIBC, exhibited a nonlinear relationship with PMI by the RCS model adjusted by age, gender, and history of diabetes.
Clinically Meaningful Outcomes after 1 Year of Treatment with Setmelanotide in an Adult Patient with a Variant in SH2B1
Authors: Politei Juan M. , Patrono Andrea
Published: September 2024

Introduction: Monogenic obesity is caused by a unique genetic dysfunction, often appears in childhood, and can be accompanied by neuroendocrine, skeletal, developmental, and behavioral disorders, among other manifestations. Some variants in the SH2B1 gene have been suggested as strong candidates for the development of autosomal dominant obesity. Case Presentation: We describe here the clinical response after 1 year of setmelanotide treatment in a 22-year-old patient with an SH2B1 variant. After 3 months of treatment, our patient lost 5.4% of body weight. This period was followed by a 3-month period of noncompliance, in which the patient gained 4% body weight. After reinstating daily drug administration, the patient showed a 19.5% reduction in body weight and a clear improvement in all hunger scales after 1 year of treatment. Conclusion: These results indicate that the changes seen are drug dependent and provide positive evidence for the administration of setmelanotide in adult patients with heterozygous variants in the SH2B1 gene.