bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplementary Figures S1-S13 from Cell-Free Urine and Plasma DNA Mutational Analysis Predicts Neoadjuvant Chemotherapy Response and Outcome in Patients with Muscle-Invasive Bladder Cancer
Authors: Christensen Emil , Nordentoft Iver , Birkenkamp-Demtröder Karin , Elbæk Sara K. , Lindskrog Sia V. , Taber Ann , Andreasen Tine G. , Strandgaard Trine , Knudsen Michael , Lamy Philippe , Agerbæk Mads , Jensen Jørgen B. , Dyrskjøt Lars
Published: April 2023

Supplementary Fig. 1. Overview of sample availability and in-silico analysis of the limit of detection for the applied methodology.Supplementary Fig. 2. Comparison between mutations observed in primary and residual tumors at radical cystectomy (RC).Supplementary Fig. 3. Mean sample VAF levels for plasma, urine pellet and urine supernatant split by tdDNA call status in other paired sample types from the same clinical visit.Supplementary Fig. 4. Association between mean sample VAF.Supplementary Fig. 5. Association between mean VAFSupplementary Fig. 6. Urine dipstick measurements compared to the amount of DNA extracted from urine supernatants collected at the same time (+/- 1 day).Supplementary Fig. 7. Urine dipstick measurements compared to the urinary tumor DNA (utDNA) call status in urine supernatants collected at the same time (+/- 1 day).Supplementary Fig. 8. Urine dipstick measurements compared to the urinary tumor DNA (utDNA) level in urine supernatants collected at the same time (+/- 1 day).Supplementary Fig. 9. Mean sample VAF levels for all patients with detectable tumor DNA split by sample type. Tumor stage evaluation was based on the TURB specimen and tumor DNA level based on samples collected before TURB.Supplementary Fig. 10. Kaplan-Meier survival analysis of recurrence-free survival (RFS) stratified by tumor DNA status for all sample types.Supplementary Fig. 11. Tumor DNA levels compared to NAC response.Supplementary Fig. 12. Kaplan-Meier survival analysis of recurrence-free survival (RFS) stratified by tumor DNA level for all sample types.Supplementary Fig. 13. a-b) Association between tumor DNA dynamics and neoadjuvant chemotherapy (NAC) response for a) urine pellet and b) urine supernatant. Tumor DNA clearance was defined as tumor DNA going from detectable to non-detectable and tumor DNA remains was defined as tumor DNA remaining detectable. c-d) Kaplan-Meier survival analysis of tumor DNA dynamics groups and recurrence-free survival (RFS) for c) urine pellet and d) urine supernatant.
Supplementary Table S4 from Addition of Losartan to FOLFIRINOX and Chemoradiation Reduces Immunosuppression-Associated Genes, Tregs, and FOXP3+ Cancer Cells in Locally Advanced Pancreatic Cancer
Authors: Boucher Yves , Posada Jessica M. , Subudhi Sonu , Kumar Ashwin S. , Rosario Spencer R. , Gu Liqun , Kumra Heena , Mino-Kenudson Mari , Talele Nilesh P. , Duda Dan G. , Fukumura Dai , Wo Jennifer Y. , Clark Jeffrey W. , Ryan David P. , Fernandez-Del Castillo Carlos , Hong Theodore S. , Pittet Mikael J. , Jain Rakesh K.
Published: April 2023

Gene sets associated with overall survival in losartan+FFX+CRT and FFX+CRT-treated groups.
Supplementary Table S2 from Addition of Losartan to FOLFIRINOX and Chemoradiation Reduces Immunosuppression-Associated Genes, Tregs, and FOXP3+ Cancer Cells in Locally Advanced Pancreatic Cancer
Authors: Boucher Yves , Posada Jessica M. , Subudhi Sonu , Kumar Ashwin S. , Rosario Spencer R. , Gu Liqun , Kumra Heena , Mino-Kenudson Mari , Talele Nilesh P. , Duda Dan G. , Fukumura Dai , Wo Jennifer Y. , Clark Jeffrey W. , Ryan David P. , Fernandez-Del Castillo Carlos , Hong Theodore S. , Pittet Mikael J. , Jain Rakesh K.
Published: April 2023

Top 30 upregulated and 30 downregulated genes in treatment group versus untreated.
Supplementary Figure S4 from Addition of Losartan to FOLFIRINOX and Chemoradiation Reduces Immunosuppression-Associated Genes, Tregs, and FOXP3+ Cancer Cells in Locally Advanced Pancreatic Cancer
Authors: Boucher Yves , Posada Jessica M. , Subudhi Sonu , Kumar Ashwin S. , Rosario Spencer R. , Gu Liqun , Kumra Heena , Mino-Kenudson Mari , Talele Nilesh P. , Duda Dan G. , Fukumura Dai , Wo Jennifer Y. , Clark Jeffrey W. , Ryan David P. , Fernandez-Del Castillo Carlos , Hong Theodore S. , Pittet Mikael J. , Jain Rakesh K.
Published: April 2023

Quantitative analysis of immunofluorescence staining in PDAC lesions from FFX+CRT and losartan+FFX+CRT-treated groups.
Supplementary Table S2 from Biomarker Data from the Phase III KATHERINE Study of Adjuvant T-DM1 versus Trastuzumab for Residual Invasive Disease after Neoadjuvant Therapy for HER2-Positive Breast Cancer
Authors: Denkert Carsten , Lambertini Chiara , Fasching Peter A. , Pogue-Geile Katherine L. , Mano Max S. , Untch Michael , Wolmark Norman , Huang Chiun-Sheng , Loibl Sibylle , Mamounas Eleftherios P. , Geyer Charles E. , Lucas Peter C. , Boulet Thomas , Song Chunyan , Lewis Gail D. , Nowicka Malgorzata , de Haas Sanne , Basik Mark
Published: April 2023

Prognostic value for IDFS by treatment arm of biomarker gene expression levels (>median vs. ≤median and continuous) in post-NAT surgical RNA-evaluable tissue samples. Analysis is adjusted for tumor content. One sample could not be included because there was insufficient information on tumor content.
Supplementary Table S1 from Biomarker Data from the Phase III KATHERINE Study of Adjuvant T-DM1 versus Trastuzumab for Residual Invasive Disease after Neoadjuvant Therapy for HER2-Positive Breast Cancer
Authors: Denkert Carsten , Lambertini Chiara , Fasching Peter A. , Pogue-Geile Katherine L. , Mano Max S. , Untch Michael , Wolmark Norman , Huang Chiun-Sheng , Loibl Sibylle , Mamounas Eleftherios P. , Geyer Charles E. , Lucas Peter C. , Boulet Thomas , Song Chunyan , Lewis Gail D. , Nowicka Malgorzata , de Haas Sanne , Basik Mark
Published: April 2023

Comparison of baseline patient and disease characteristics assessed at eligibility in the ITT population versus in those with mRNA data derived from pre-NAT or post-NAT surgical samples (RNA-evaluable population). Note: the pre-NAT and post-NAT samples are not paired.
Supplementary Table S5 from The Oral PI3Kδ Inhibitor Linperlisib for the Treatment of Relapsed and/or Refractory Follicular Lymphoma: A Phase II, Single-Arm, Open-Label Clinical Trial
Authors: Wang Tingyu , Sun Xiuhua , Qiu Lihua , Su Hang , Cao Junning , Li Zhiming , Song Yuqin , Zhang Li , Li Dengju , Wu Huijing , Zhang Wei , Li Junmin , Zhou Keshu , Zhou Hui , Yang Yu , Li Zhifeng , Cen Hong , Cai Zhen , Zhang Zhihui , Fu Weijun , Jin Jie , Li Fei , Wu Weixin , Gu Xuekui , Zhu Weiliang , Liu Lihong , Li Zengjun , Yi Shuhua , Bao Hanying , Xu Zusheng , Qiu Lugui
Published: April 2023

Number and frequency of TRAE that led to discontinuation from the trial
Supplementary Table S3 from The Oral PI3Kδ Inhibitor Linperlisib for the Treatment of Relapsed and/or Refractory Follicular Lymphoma: A Phase II, Single-Arm, Open-Label Clinical Trial
Authors: Wang Tingyu , Sun Xiuhua , Qiu Lihua , Su Hang , Cao Junning , Li Zhiming , Song Yuqin , Zhang Li , Li Dengju , Wu Huijing , Zhang Wei , Li Junmin , Zhou Keshu , Zhou Hui , Yang Yu , Li Zhifeng , Cen Hong , Cai Zhen , Zhang Zhihui , Fu Weijun , Jin Jie , Li Fei , Wu Weixin , Gu Xuekui , Zhu Weiliang , Liu Lihong , Li Zengjun , Yi Shuhua , Bao Hanying , Xu Zusheng , Qiu Lugui
Published: April 2023

Representativeness of Study Participants
Supplementary Figure S2 from Biomarker Data from the Phase III KATHERINE Study of Adjuvant T-DM1 versus Trastuzumab for Residual Invasive Disease after Neoadjuvant Therapy for HER2-Positive Breast Cancer
Authors: Denkert Carsten , Lambertini Chiara , Fasching Peter A. , Pogue-Geile Katherine L. , Mano Max S. , Untch Michael , Wolmark Norman , Huang Chiun-Sheng , Loibl Sibylle , Mamounas Eleftherios P. , Geyer Charles E. , Lucas Peter C. , Boulet Thomas , Song Chunyan , Lewis Gail D. , Nowicka Malgorzata , de Haas Sanne , Basik Mark
Published: April 2023

Comparison of HER2 expression heterogeneity in paired pre-NAT (i.e., before surgery) and post-NAT surgical samples. Patients were categorized according to whether HER2 staining was focal (<30%), heterogeneous (30–79%), or homogeneous (≥80%) based on the total percentage of cells stained with 2+ and 3+ intensity. IHC, immunohistochemistry; NAT, neoadjuvant therapy.
Supplementary Table S2 from The Oral PI3Kδ Inhibitor Linperlisib for the Treatment of Relapsed and/or Refractory Follicular Lymphoma: A Phase II, Single-Arm, Open-Label Clinical Trial
Authors: Wang Tingyu , Sun Xiuhua , Qiu Lihua , Su Hang , Cao Junning , Li Zhiming , Song Yuqin , Zhang Li , Li Dengju , Wu Huijing , Zhang Wei , Li Junmin , Zhou Keshu , Zhou Hui , Yang Yu , Li Zhifeng , Cen Hong , Cai Zhen , Zhang Zhihui , Fu Weijun , Jin Jie , Li Fei , Wu Weixin , Gu Xuekui , Zhu Weiliang , Liu Lihong , Li Zengjun , Yi Shuhua , Bao Hanying , Xu Zusheng , Qiu Lugui
Published: April 2023

Detailed inclusion and exclusion criteria for the clinical trial (NCT04370405)
Supplementary Figure S1 from Biomarker Data from the Phase III KATHERINE Study of Adjuvant T-DM1 versus Trastuzumab for Residual Invasive Disease after Neoadjuvant Therapy for HER2-Positive Breast Cancer
Authors: Denkert Carsten , Lambertini Chiara , Fasching Peter A. , Pogue-Geile Katherine L. , Mano Max S. , Untch Michael , Wolmark Norman , Huang Chiun-Sheng , Loibl Sibylle , Mamounas Eleftherios P. , Geyer Charles E. , Lucas Peter C. , Boulet Thomas , Song Chunyan , Lewis Gail D. , Nowicka Malgorzata , de Haas Sanne , Basik Mark
Published: April 2023

Comparison of HER2 expression intensity in paired pre-NAT (i.e., before surgery) and post-NAT surgical samples. HER2, human epidermal growth factor receptor 2; IHC, immunohistochemistry; NAT, neoadjuvant therapy.
Supplementary Figure S9 from Better than RECIST and Faster than iRECIST: Defining the Immunotherapy Progression Decision Score to Better Manage Progressive Tumors on Immunotherapy
Authors: Belkouchi Younes , Talbot Hugues , Lassau Nathalie , Lawrance Littisha , Farhane Siham , Feki-Mkaouar Rahma , Hadchiti Joya , Dawi Lama , Vibert Julien , Cournède Paul-Henry , Cousteix Clara , Mazza Camille , Kind Michele , Italiano Antoine , Marabelle Aurelien , Ammari Samy , Champiat Stephane
Published: April 2023

Survival of pseudo-PD vs confirmed PD in our cohort.
Supplementary Figures S1-S4 from A Large-Scale Prospective Concordance Study of Plasma- and Tissue-Based Next-Generation Targeted Sequencing for Advanced Non–Small Cell Lung Cancer (LC-SCRUM-Liquid)
Authors: Sugimoto Akira , Matsumoto Shingo , Udagawa Hibiki , Itotani Ryo , Usui Yuko , Umemura Shigeki , Nishino Kazumi , Nakachi Ichiro , Kuyama Shoichi , Daga Haruko , Hara Satoshi , Miyamoto Shingo , Kato Terufumi , Sakakibara-Konishi Jun , Tabata Eriko , Nakagawa Taku , Kawaguchi Tomoya , Sakai Tetsuya , Shibata Yuji , Izumi Hiroki , Nosaki Kaname , Zenke Yoshitaka , Yoh Kiyotaka , Goto Koichi
Published: April 2023

Supplementary Figure S1. Consort diagram.
Supplementary Figure S2. Frequency of the targetable gene alterations detected by plasma cfDNA sequencing (A) and
tissue assay (B) in squamous cell carcinoma
Supplementary Figure S3. Positive percent agreement of plasma cfDNA sequencing compared to tissue assay according to
patient characteristics.
PPA, positive percent agreement.
Supplementary Figure S4. Positive percent agreement of plasma cfDNA sequencing compared to tissue assay according to
metastatic site.
PPA, positive percent agreement.
Supplementary Figure S1 from Better than RECIST and Faster than iRECIST: Defining the Immunotherapy Progression Decision Score to Better Manage Progressive Tumors on Immunotherapy
Authors: Belkouchi Younes , Talbot Hugues , Lassau Nathalie , Lawrance Littisha , Farhane Siham , Feki-Mkaouar Rahma , Hadchiti Joya , Dawi Lama , Vibert Julien , Cournède Paul-Henry , Cousteix Clara , Mazza Camille , Kind Michele , Italiano Antoine , Marabelle Aurelien , Ammari Samy , Champiat Stephane
Published: April 2023

Distribution of primary cancer types in the development set (n=107).
Supplementary Figure S4 from Small-Molecule Polθ Inhibitors Provide Safe and Effective Tumor Radiosensitization in Preclinical Models
Authors: Rodriguez-Berriguete Gonzalo , Ranzani Marco , Prevo Remko , Puliyadi Rathi , Machado Nicole , Bolland Hannah R. , Millar Val , Ebner Daniel , Boursier Marie , Cerutti Aurora , Cicconi Alessandro , Galbiati Alessandro , Grande Diego , Grinkevich Vera , Majithiya Jayesh B. , Piscitello Desiree , Rajendra Eeson , Stockley Martin L. , Boulton Simon J. , Hammond Ester M. , Heald Robert A. , Smith Graeme C.M. , Robinson Helen M.R. , Higgins Geoff S.
Published: April 2023

Accompanies Figure 3 (Effect of ART558 under hypoxic conditions)
Supplementary Table S1 from CCNE1 and PLK1 Mediate Resistance to Palbociclib in HR+/HER2− Metastatic Breast Cancer
Authors: Guerrero-Zotano Ángel , Belli Stefania , Zielinski Christoph , Gil-Gil Miguel , Fernandez-Serra Antonio , Ruiz-Borrego Manuel , Ciruelos Gil Eva Maria , Pascual Javier , Muñoz-Mateu Montserrat , Bermejo Begoña , Margeli Vila Mireia , Antón Antonio , Murillo Laura , Nissenbaum Bella , Liu Yuan , Herranz Jesús , Fernández-García Daniel , Caballero Rosalía , López-Guerrero José Antonio , Bianco Roberto , Formisano Luigi , Turner Nicholas , Martín Miguel
Published: April 2023

List of 51 genes differentially expressed in tumors, grouped by sensitive or refractory to palbociclib plus ET. Controlling the FDR at 5% with the q-value method (SAM)
Supplementary Table S8 from Blood-Based Diagnosis and Risk Stratification of Patients with Pancreatic Intraductal Papillary Mucinous Neoplasm (IPMN)
Authors: Zhang Chaoyang , Al-Shaheri Fawaz N. , Alhamdani Mohamed Saiel Saeed , Bauer Andrea S. , Hoheisel Jörg D. , Schenk Miriam , Hinz Ulf , Goedecke Philipp , Al-Halabi Karam , Büchler Markus W. , Giese Nathalia A. , Hackert Thilo , Roth Susanne
Published: April 2023

List of combined protein-miRNA classifiers.
Supplementary Figure S6 from CCNE1 and PLK1 Mediate Resistance to Palbociclib in HR+/HER2− Metastatic Breast Cancer
Authors: Guerrero-Zotano Ángel , Belli Stefania , Zielinski Christoph , Gil-Gil Miguel , Fernandez-Serra Antonio , Ruiz-Borrego Manuel , Ciruelos Gil Eva Maria , Pascual Javier , Muñoz-Mateu Montserrat , Bermejo Begoña , Margeli Vila Mireia , Antón Antonio , Murillo Laura , Nissenbaum Bella , Liu Yuan , Herranz Jesús , Fernández-García Daniel , Caballero Rosalía , López-Guerrero José Antonio , Bianco Roberto , Formisano Luigi , Turner Nicholas , Martín Miguel
Published: April 2023

PALOMA-3 study as validation dataset
Supplementary Figure S4 from CCNE1 and PLK1 Mediate Resistance to Palbociclib in HR+/HER2− Metastatic Breast Cancer
Authors: Guerrero-Zotano Ángel , Belli Stefania , Zielinski Christoph , Gil-Gil Miguel , Fernandez-Serra Antonio , Ruiz-Borrego Manuel , Ciruelos Gil Eva Maria , Pascual Javier , Muñoz-Mateu Montserrat , Bermejo Begoña , Margeli Vila Mireia , Antón Antonio , Murillo Laura , Nissenbaum Bella , Liu Yuan , Herranz Jesús , Fernández-García Daniel , Caballero Rosalía , López-Guerrero José Antonio , Bianco Roberto , Formisano Luigi , Turner Nicholas , Martín Miguel
Published: April 2023

Progression Free Survival analysis on CCNE1 expression levels under palbociclib plus ET treatment
Supplementary Figure S2 from CCNE1 and PLK1 Mediate Resistance to Palbociclib in HR+/HER2− Metastatic Breast Cancer
Authors: Guerrero-Zotano Ángel , Belli Stefania , Zielinski Christoph , Gil-Gil Miguel , Fernandez-Serra Antonio , Ruiz-Borrego Manuel , Ciruelos Gil Eva Maria , Pascual Javier , Muñoz-Mateu Montserrat , Bermejo Begoña , Margeli Vila Mireia , Antón Antonio , Murillo Laura , Nissenbaum Bella , Liu Yuan , Herranz Jesús , Fernández-García Daniel , Caballero Rosalía , López-Guerrero José Antonio , Bianco Roberto , Formisano Luigi , Turner Nicholas , Martín Miguel
Published: April 2023

Patients’ characteristics and Progression Free Survival comparison. Biomarker Cohort and PEARL Study Population
Supplementary Figure S11 from CCNE1 and PLK1 Mediate Resistance to Palbociclib in HR+/HER2− Metastatic Breast Cancer
Authors: Guerrero-Zotano Ángel , Belli Stefania , Zielinski Christoph , Gil-Gil Miguel , Fernandez-Serra Antonio , Ruiz-Borrego Manuel , Ciruelos Gil Eva Maria , Pascual Javier , Muñoz-Mateu Montserrat , Bermejo Begoña , Margeli Vila Mireia , Antón Antonio , Murillo Laura , Nissenbaum Bella , Liu Yuan , Herranz Jesús , Fernández-García Daniel , Caballero Rosalía , López-Guerrero José Antonio , Bianco Roberto , Formisano Luigi , Turner Nicholas , Martín Miguel
Published: April 2023

Volasertib overcomes resistance to fulvestrant and palbociclib in PLK1-overexpressing ER+ breast cancer cells
Supplementary Figure S10 from CCNE1 and PLK1 Mediate Resistance to Palbociclib in HR+/HER2− Metastatic Breast Cancer
Authors: Guerrero-Zotano Ángel , Belli Stefania , Zielinski Christoph , Gil-Gil Miguel , Fernandez-Serra Antonio , Ruiz-Borrego Manuel , Ciruelos Gil Eva Maria , Pascual Javier , Muñoz-Mateu Montserrat , Bermejo Begoña , Margeli Vila Mireia , Antón Antonio , Murillo Laura , Nissenbaum Bella , Liu Yuan , Herranz Jesús , Fernández-García Daniel , Caballero Rosalía , López-Guerrero José Antonio , Bianco Roberto , Formisano Luigi , Turner Nicholas , Martín Miguel
Published: April 2023

Evaluation of volasertib effects on tumor spheroid growth and on the activation of signal transduction pathways in PalboR and FPR cells
Supplementary figure 4: PFS and OS by ajcc8 from Concurrent Definitive Immunoradiotherapy for Patients with Stage III–IV Head and Neck Cancer and Cisplatin Contraindication
Authors: Weiss Jared , Sheth Siddharth , Deal Allison M. , Grilley Olson Juneko E. , Patel Samip , Hackman Trevor G. , Blumberg Jeffrey M. , Galloway Thomas J. , Patel Shetal , Zanation Adam M. , Shen Colette J. , Hayes D. Neil , Hilliard Christopher , Mehra Ranee , McKinnon Karen P. , Wang Hsing-Hui , Weissler Mark Christian , Bauman Jessica R. , Chera Bhishamjit S. , Vincent Benjamin G.
Published: April 2023

PFS and OS by AJCC 8
Supplementary Figure 2: T cell gating from Concurrent Definitive Immunoradiotherapy for Patients with Stage III–IV Head and Neck Cancer and Cisplatin Contraindication
Authors: Weiss Jared , Sheth Siddharth , Deal Allison M. , Grilley Olson Juneko E. , Patel Samip , Hackman Trevor G. , Blumberg Jeffrey M. , Galloway Thomas J. , Patel Shetal , Zanation Adam M. , Shen Colette J. , Hayes D. Neil , Hilliard Christopher , Mehra Ranee , McKinnon Karen P. , Wang Hsing-Hui , Weissler Mark Christian , Bauman Jessica R. , Chera Bhishamjit S. , Vincent Benjamin G.
Published: April 2023

T cell gating
Supplementary Data from Concurrent Definitive Immunoradiotherapy for Patients with Stage III–IV Head and Neck Cancer and Cisplatin Contraindication
Authors: Weiss Jared , Sheth Siddharth , Deal Allison M. , Grilley Olson Juneko E. , Patel Samip , Hackman Trevor G. , Blumberg Jeffrey M. , Galloway Thomas J. , Patel Shetal , Zanation Adam M. , Shen Colette J. , Hayes D. Neil , Hilliard Christopher , Mehra Ranee , McKinnon Karen P. , Wang Hsing-Hui , Weissler Mark Christian , Bauman Jessica R. , Chera Bhishamjit S. , Vincent Benjamin G.
Published: April 2023

Supplementary tables
Supplementary Data from Concurrent Definitive Immunoradiotherapy for Patients with Stage III–IV Head and Neck Cancer and Cisplatin Contraindication
Authors: Weiss Jared , Sheth Siddharth , Deal Allison M. , Grilley Olson Juneko E. , Patel Samip , Hackman Trevor G. , Blumberg Jeffrey M. , Galloway Thomas J. , Patel Shetal , Zanation Adam M. , Shen Colette J. , Hayes D. Neil , Hilliard Christopher , Mehra Ranee , McKinnon Karen P. , Wang Hsing-Hui , Weissler Mark Christian , Bauman Jessica R. , Chera Bhishamjit S. , Vincent Benjamin G.
Published: April 2023

Protocol
Data from Single-Cell Transcriptomics Reveals Immune Reconstitution in Patients with R/R T-ALL/LBL Treated with Donor-Derived CD7 CAR-T Therapy
Authors: Chen Wei , Shi Hui , Liu Zhuojun , Yang Fan , Liu Jia , Zhang Leqiang , Wu Yajin , Xia Yuanshi , Ou Yuxuan , Li Ruiting , Zhang Ting , Zhang Jiecheng , Ke Xiaoyan , Hu Kai , Yu Jian
Published: April 2023

AbstractPurpose:
CD7 chimeric antigen receptor T (CAR-T) therapy has potent antitumor activity against relapsed/refractory (R/R) T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL), however, immune reconstitution after CAR-T remains largely unknown.
Patients and Methods:
An open-label phase I clinical trial (ChiCTR2200058969) was initiated to evaluate safety and efficacy of donor-derived CD7 CAR-T cells in 7 R/R T-ALL/LBL patients. CAR-T cells were detected by flow cytometry and PCR. Cytokine levels were quantified by cytometric bead arrays. Single-cell RNA sequencing (scRNA-seq) was adopted to profile immune reconstitution.
Results:
Optimal complete remission (CR) was 100% on day 28, and median followed-up time was 4 months. Leukopenia, thrombocytopenia, and neutropenia were observed in 6 patients, and infections occurred in 5 patients. Two patients died of serious infection and one died of a brain hemorrhage. CAR-T cells expanded efficiently in all patients. CD7+ T cells were eliminated in peripheral blood on day 11 after infusion, and CD7− T cells dramatically expanded in all patients. scRNA-seq suggested that immunologic activities of CD7− T cells were stronger than those of T cells before infusion due to higher expression levels of T-cell function-related pathways, and major characters of such CD7− T cells were activation of autoimmune-related pathways. Monocyte loss was found in 2 patients who died of serious infections, indicating the main cause of the infections after infusion. S100A8 and S100A9 were identified as potential relapse markers due to their notable upregulation in leukocyte lineage in relapsed patients versus non-relapse controls.
Conclusions:
Our data revealed cellular level dynamics of immune homeostasis of CD7 CAR-T therapy, which is valuable for optimizing the treatment of R/R T-ALL/LBL.
Data from Impact of Genomic and Clinical Factors on Outcome of Children ≥18 Months of Age with Stage 3 Neuroblastoma with Unfavorable Histology and without MYCN Amplification: A Children's Oncology Group (COG) Report
Authors: Pinto Navin , Naranjo Arlene , Ding Xiangming , Zhang Fan F. , Hibbitts Emily , Kennedy Rebekah , Tibbetts Rachelle , Wong-Michalak Shannon , Craig David W. , Manojlovic Zarko , Hogarty Michael D. , Kreissman Susan , Bagatell Rochelle , Irwin Meredith S. , Park Julie R. , Asgharzadeh Shahab
Published: April 2023

AbstractPurpose:
Patients ≥18 months of age with International Neuroblastoma Staging System (INSS) stage 3 unfavorable histology (UH), MYCN-nonamplified (MYCN-NA) tumors have favorable survival rates compared with other high-risk neuroblastoma populations. The impact of select clinical and biological factors on overall survival (OS) and event-free survival (EFS) were evaluated.
Experimental Design:
Patients enrolled on Children's Oncology Group (COG) A3973 (n = 34), ANBL0532 (n = 27), and/or biology protocol ANBL00B1 (n = 72) were analyzed. Tumors with available DNA (n = 65) and RNA (n = 42) were subjected to whole-exome sequencing (WES) and RNA sequencing. WES analyses and gene expression profiling were evaluated for their impact on survival. Multivariate analyses of EFS/OS using significant factors from univariate analyses were performed.
Results:
5-year EFS/OS for patients treated with high-risk therapy on A3973 and ANBL0532 were 73.0% ± 8.1%/87.9% ± 5.9% and 61.4% ± 10.2%/73.0% ± 9.2%, respectively (P = 0.1286 and P = 0.2180). In the A3973/ANBL0532 cohort, patients with less than partial response (PR; n = 5) at end-induction had poor outcomes (5-year EFS/OS: 0%/20.0% ± 17.9%. Univariate analyses of WES data revealed that subjects whose tumors had chromosome 1p or 11q loss/LOH and chromosome 5 or 9 segmental chromosomal aberrations had inferior EFS compared with those with tumors without these aberrations. Multivariate analysis revealed that 11q loss/LOH was an independent predictor of inferior OS [HR, 3.116 (95% confidence interval, 1.034–9.389), P = 0.0435].
Conclusions:
Patients ≥18 months of age at diagnosis who had tumors with UH and MYCN-NA INSS stage 3 neuroblastoma assigned to high-risk therapy had an 81.6% ± 5.3% 5-year OS. Less than PR to induction therapy and chromosome 11q loss/LOH are independent predictors of inferior outcome and identify patients who should be eligible for future high-risk clinical trials.
Data from Better than RECIST and Faster than iRECIST: Defining the Immunotherapy Progression Decision Score to Better Manage Progressive Tumors on Immunotherapy
Authors: Belkouchi Younes , Talbot Hugues , Lassau Nathalie , Lawrance Littisha , Farhane Siham , Feki-Mkaouar Rahma , Hadchiti Joya , Dawi Lama , Vibert Julien , Cournède Paul-Henry , Cousteix Clara , Mazza Camille , Kind Michele , Italiano Antoine , Marabelle Aurelien , Ammari Samy , Champiat Stephane
Published: April 2023

AbstractPurpose:
The objective of the study is to propose the immunotherapy progression decision (iPD) score, a practical tool based on patient features that are available at the first evaluation of immunotherapy treatment, to help oncologists decide whether to continue the treatment or switch rapidly to another therapeutic line when facing a progressive disease patient at the first evaluation.
Experimental Design:
This retrospective study included 107 patients with progressive disease at first evaluation according to RECIST 1.1. Clinical, radiological, and biological data at baseline and first evaluation were analyzed. An external validation set consisting of 31 patients with similar baseline characteristics was used for the validation of the score.
Results:
Variables were analyzed in a univariate study. The iPD score was constructed using only independent variables, each considered as a worsening factor for the survival of patients. The patients were stratified in three groups: good prognosis (GP), poor prognosis (PP), and critical prognosis (CP). Each group showed significantly different survivals (GP: 11.4, PP: 4.4, CP: 2.3 months median overall survival, P < 0.001, log-rank test). Moreover, the iPD score was able to detect the pseudoprogressors better than other scores. On the validation set, CP patients had significantly worse survival than PP and GP patients (P < 0.05, log-rank test).
Conclusions:
The iPD score provides oncologists with a new evaluation, computable at first progression, to decide whether treatment should be continued (for the GP group), or immediately changed for the PP and CP groups. Further validation on larger cohorts is needed to prove its efficacy in clinical practice.
Data from Phase I Study of the Liposomal Formulation of Eribulin (E7389-LF): Results from the Advanced Gastric Cancer Expansion Cohort
Authors: Shitara Kohei , Hirao Motohiro , Iwasa Satoru , Oshima Takashi , Komatsu Yoshito , Kawazoe Akihito , Sato Yasuyoshi , Hamakawa Takuya , Yonemori Kan , Machida Nozomu , Yuki Satoshi , Suzuki Takuya , Okumura Shiori , Takase Takao , Semba Taro , Zimmermann Bob , Teng Angela , Yamaguchi Kensei
Published: April 2023

AbstractPurpose:
In the dose-expansion part of this open-label, phase I study, we explored the efficacy and safety of E7389-LF (liposomal formulation of eribulin) in Japanese patients with advanced gastric cancer.
Patients and Methods:
Patients with advanced gastric cancer who had been previously treated with ≥2 lines of chemotherapy received E7389-LF 2.0 mg/m2 every 3 weeks (the previously determined maximum tolerated dose, the primary objective of Study 114). Secondary objectives included objective response rate (ORR), progression-free survival (PFS), and safety; exploratory objectives included disease control rate (DCR) and clinical benefit rate (CBR), as well as pharmacodynamic measurements of serum biomarkers.
Results:
As of June 24, 2021, 34 patients were enrolled and treated (10 from the original dose-expansion cohort, expanded to include 24 additional patients). Six patients had partial responses, for an ORR of 17.6% [95% confidence interval (CI), 6.8–34.5], and the median PFS was 3.7 months (95% CI, 2.7–4.8). The DCR was 79.4% (95% CI, 62.1–91.3), and the CBR was 32.4% (95% CI, 17.4–50.5). Overall, 32 patients (94.1%) experienced treatment-related adverse events, and 26 patients (76.5%) experienced grade ≥3 events, most commonly neutropenia (41.2%) and leukopenia (29.4%). Of the 8 endothelial cell/vasculature markers tested in this study, 7 were significantly increased among patients treated with E7389-LF; these changes were generally consistent regardless of best overall response.
Conclusions:
E7389-LF 2.0 mg/m2 every 3 weeks was tolerable and showed preliminary activity for the treatment of patients with gastric cancer.
Data from Genomic and Transcriptomic Characteristics of Metastatic Thyroid Cancers with Exceptional Responses to Radioactive Iodine Therapy
Authors: Boucai Laura , Saqcena Mahesh , Kuo Fengshen , Grewal Ravinder K. , Socci Nicholas , Knauf Jeffrey A. , Krishnamoorthy Gnana P. , Ryder Mabel , Ho Alan L. , Ghossein Ronald A. , Morris Luc G.T. , Seshan Venkatraman , Fagin James A.
Published: April 2023

AbstractPurpose:
The determinants of response or resistance to radioiodine (RAI) are unknown. We aimed to identify genomic and transcriptomic factors associated with structural responses to RAI treatment of metastatic thyroid cancer, which occur infrequently, and to test whether high MAPK pathway output was associated with RAI refractoriness.
Experimental Design:
Exceptional response to RAI was defined as reduction of tumor volume based on RECIST v1.1. We performed a retrospective case–control study of genomic and transcriptomic characteristics of exceptional responders (ER; n = 8) versus nonresponders (NR; n = 16) matched by histologic type and stage at presentation on a 1:2 ratio.
Results:
ER are enriched for mutations that activate MAPK through RAF dimerization (RAS, class 2 BRAF, RTK fusions), whereas NR are associated with BRAFV600E, which signals as a monomer and is unresponsive to negative feedback. ER have a lower MAPK transcriptional output and a higher thyroid differentiation score (TDS) than NR (P < 0.05). NR are enriched for 1q-gain (P < 0.05) and mutations of genes regulating mRNA splicing and the PI3K pathway. BRAFV600E tumors with 1q-gain have a lower TDS than BRAFV600E/1q-quiet tumors and transcriptomic signatures associated with metastatic propensity.
Conclusions:
ER tumors have a lower MAPK output and higher TDS than NR, whereas NR have a high frequency of BRAFV600E and 1q-gain. Molecular profiling of thyroid cancers and further functional validation of the key findings discriminating ER from NR may help predict response to RAI therapy.
Data from Biomarker Data from the Phase III KATHERINE Study of Adjuvant T-DM1 versus Trastuzumab for Residual Invasive Disease after Neoadjuvant Therapy for HER2-Positive Breast Cancer
Authors: Denkert Carsten , Lambertini Chiara , Fasching Peter A. , Pogue-Geile Katherine L. , Mano Max S. , Untch Michael , Wolmark Norman , Huang Chiun-Sheng , Loibl Sibylle , Mamounas Eleftherios P. , Geyer Charles E. , Lucas Peter C. , Boulet Thomas , Song Chunyan , Lewis Gail D. , Nowicka Malgorzata , de Haas Sanne , Basik Mark
Published: April 2023

AbstractPurpose:
In KATHERINE, adjuvant T-DM1 reduced risk of disease recurrence or death by 50% compared with trastuzumab in patients with residual invasive breast cancer after neoadjuvant therapy (NAT) comprised of HER2-targeted therapy and chemotherapy. This analysis aimed to identify biomarkers of response and differences in biomarker expression before and after NAT.
Experimental Design:
Exploratory analyses investigated the relationship between invasive disease-free survival (IDFS) and HER2 protein expression/gene amplification, PIK3CA hotspot mutations, and gene expression of HER2, PD-L1, CD8, predefined immune signatures, and Prediction Analysis of Microarray 50 intrinsic molecular subtypes, classified by Absolute Intrinsic Molecular Subtyping. HER2 expression on paired pre- and post-NAT samples was examined.
Results:
T-DM1 appeared to improve IDFS versus trastuzumab across most biomarker subgroups, except the HER2 focal expression subgroup. High versus low HER2 gene expression in residual disease was associated with worse outcomes with trastuzumab [HR, 2.02; 95% confidence interval (CI), 1.32–3.11], but IDFS with T-DM1 was independent of HER2 expression level (HR, 1.01; 95% CI, 0.56–1.83). Low PD-L1 gene expression in residual disease was associated with worse outcomes with trastuzumab (HR, 0.66; 95% CI, 0.44–1.00), but not T-DM1 (HR, 1.05; 95% CI, 0.59–1.87). PIK3CA mutations were not prognostic. Increased variability in HER2 expression was observed in post-NAT versus paired pre-NAT samples.
Conclusions:
T-DM1 appears to overcome HER2 resistance. T-DM1 benefit does not appear dependent on immune activation, but these results do not rule out an influence of the tumor immune microenvironment on the degree of response.
Abstract LB090: IL-18 secreting chimeric antigen receptor T cells targeting glypican-3show superior persistence and antitumor immunity against hepatocellular carcinoma
Authors: Jeong Joseph H. , Chang Young-Kyun , Kang You-Yeon , Lee Jeong-Yun , Lee Sae-Rom , Lee Yun-Kyung , Kim Young-Ho , Kwon Byoung S.
Published: April 2023

Over the last decade, immunotherapy has revolutionized the way we treat cancer primarily by boosting the body’s own immune system to help fight cancer. In particular, an engineered T cell therapy, namely chimeric antigen receptor (CAR) T cell therapy, is a more aggressive way to modify T cells to recognize cancer cells and destroy them. Although these CAR-T therapies have shown remarkable clinical responses in patients with hematological malignancies, their efficacy in solid tumor treatment has been disappointing due to many challenges: lack of tumor-specific antigen targets, loss of the CAR T-cell persistence, the inability of CAR-T cells to effectively infiltrate into solid tumors, toxicities of cytokine release syndrome and neurologic toxicity, and the immunosuppressive tumor microenvironment (TME). In this regard, we report here that we have successfully developed a CAR-T cell therapy, referred to as EU307, to treat one type of solid tumor, hepatocellular carcinoma (HCC). EU307 is a fourth-generation CAR-T therapy that targets the HCC-specific tumor antigen of glypican-3 (GPC3), and also secretes IL-18 which results in autocrine co-stimulation of CAR-T cells and reprogramming of the TME into a tumor-killing environment. Through a sophistically optimized manufacturing process in our good manufacturing practices (GMP) facility, we are able to manufacture CAR-T cells with stem cell memory (TSCM) and central memory (TCM) phenotypes. Functionally, EU307, when infused with as little as 0.1 × 106 total cells per animal, showed superior in vivo persistence and antitumor immunity in an HCC tumor-bearing mouse model. Furthermore, a single dose toxicity study in the same disease mouse model determined the no observed adverse effect level (NOAEL) as 5.0 × 105 total cells per male and 1.0 × 106 total cells per female. Taken together, our studies demonstrate that we have a developed a novel fourth-generation CAR-T therapy to treat HCC, a solid tumor that expresses a high-level of tumor-specific GPC3, by overcoming previously limiting factors in the development of CAR-T therapies against solid tumors.

Citation Format: Joseph H. Jeong, Young-Kyun Chang, You-Yeon Kang, Jeong-Yun Lee, Sae-Rom Lee, Yun-Kyung Lee, Young-Ho Kim, Byoung S. Kwon. IL-18 secreting chimeric antigen receptor T cells targeting glypican-3show superior persistence and antitumor immunity against hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB090.
Abstract LB096: IL15-engineered tumor infiltrating lymphocytes (cytoTIL15TM) exhibit activity against autologous tumor cells from multiple solid tumor indications without IL2
Authors: Pedro Kyle D. , Burga Rachel , Ocando Alonso Villasmil , Langley Meghan , Kulkarni Gauri , Ao Zheng , Primack Benjamin , Ross Theresa , Young Violet , Tchaicha Jeremy , Ols Michelle , Meulen Jan Ter
Published: April 2023

Tumor infiltrating lymphocyte (TIL) therapy has shown promising results in the treatment of metastatic melanoma. However, TIL therapy has conventionally required co-administration of IL2, which is associated with toxicity in patients. We previously showed that melanoma TILs engineered to express membrane-bound IL15 (mbIL15) under the control of the ligand acetazolamide (ACZ) can achieve IL2-independent expansion during manufacturing, antigen-independent persistence in vitro and anti-tumor efficacy in vivo. In the current study, we extend the cytoTIL15 cell therapy product concept to indications beyond melanoma including non-small cell lung cancers (NSCLC), triple-negative breast cancers (TNBC) and head and neck squamous cell carcinomas (HNSCC), tumor types which represent significant unmet medical needs, particularly in the post-checkpoint inhibitor refractory setting. TILs from primary NSCLC, HNSCC and TNBC were engineered to express mbIL15 in the presence of ACZ and expanded in the absence of IL2 using our proprietary rapid expansion protocol (REP). CytoTIL15 cells were predominantly CD8 positive, enriched for mbIL15 expression and maintained T cell receptor variable beta chain (TCRVβ) diversity throughout expansion. In vitro antigen- and cytokine-independent survival and polyfunctionality of cytoTIL15 cells was measured from cultures that included ACZ. To assess anti-tumor activity, cytoTIL15 cells were co-cultured with autologous patient-derived cell lines (PDc) or tumor digests from patient-derived xenografts (PDx), and cytotoxicity and IFNγ release into supernatant was measured. In vitro, cytoTIL15 cells + ACZ exhibited similar or increased polyfunctionality compared to unengineered TIL + IL2. Unlike unengineered TILs, cytoTIL15 cells + ACZ persisted in an antigen-free setting without IL2, were cytotoxic to autologous PDc and released IFNγ in response to autologous PDx tumor digest. Taken together, these data show that IL2-independent, fully functional cytoTIL15 cells can successfully be generated from tumors such as NSCLC, HNSCC & TNBC, which afflict large numbers of patients.

Citation Format: Kyle D. Pedro, Rachel Burga, Alonso Villasmil Ocando, Meghan Langley, Gauri Kulkarni, Zheng Ao, Benjamin Primack, Theresa Ross, Violet Young, Jeremy Tchaicha, Michelle Ols, Jan Ter Meulen. IL15-engineered tumor infiltrating lymphocytes (cytoTIL15TM) exhibit activity against autologous tumor cells from multiple solid tumor indications without IL2 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB096.
Abstract LB104: Preclinical evaluation of the role of Galectin-1 in tumor immune evasion associated mechanisms using a highly selective Galectin-1 small molecule inhibitor
Authors: Holyer Ian , Slack Rob , Petersen Kristoffer , Zetterberg Fredrik , Mackinnon Alison
Published: April 2023

Galectin-1 (Gal-1) is a β-galactoside-binding lectin that is highly expressed within the tumor microenvironment (TME) of some aggressive cancers and whose high expression correlates strongly with poor survival. Following a data mining exercise of external publication data and additional clinical biomarker datasets, we found strong evidence concluding the potential role of Gal-1 in the establishment of a fibrotic tumor stroma and mechanisms associated with tumor invasion, metastasis and angiogenesis. However, there was limited data regarding the role of Gal-1 in immune escape by tumors to make any strong conclusions/pathway reconstruction around this specific TME mechanism of action (MOA). To further strengthen the potential role of Gal-1 in tumor immune evasion we completed a series of preclinical in vivo and in vitro activities, using a highly selective Gal-1 small molecule inhibitor developed at Galecto Biotech. To examine the role of Gal-1 inhibition in vivo, we investigated the effects on tumor volume of the highly selective Gal-1 inhibitor, in a syngeneic mouse model of lung adenocarcinoma. RNA profiling of vehicle and compound treated tumors was also implemented following completion of the in-life phase. Oral administration of the Gal-1 inhibitor reduced mouse lung adenocarcinoma growth and increased the immune gene expression within the tumors, showing a strong association to that of exacerbated NK cell activity. No additional cytotoxic T cell gene changes were uncovered in the Gal-1 inhibitor treated tumors. We further evaluated the overall T cell compartment, relevant to the clinical TME setting, by stimulating human peripheral blood mononuclear cells (hPBMC’s) incubated with and without the Gal-1 inhibitor to observe the potential blockade of any known immune checkpoint inhibitor (ICI) resistance mechanisms. Interestingly, we found a variety of immune suppressive proteins to be inhibited, including IL-17, when hPBMC’s were incubated with the Gal-1 inhibitor. In summary, the data presented suggests highly selective Gal-1 inhibition could provide an effective, monotherapy (or be used in combination with ICI's) to boost immune infiltration and/or activation in the TME of lung adenocarcinoma and potentially other aggressive cancers.

Citation Format: Ian Holyer, Rob Slack, Kristoffer Petersen, Fredrik Zetterberg, Alison Mackinnon. Preclinical evaluation of the role of Galectin-1 in tumor immune evasion associated mechanisms using a highly selective Galectin-1 small molecule inhibitor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB104.
Abstract LB218: Developing a bispecific anti-ROR1 antibody drug conjugate for hematological and solid tumor treatment
Authors: Zhao Xiaobei , Zhu Jie , Wu Zhenhua , Li Jing , zhou yaqiong , Nie Lei , Chen Gang
Published: April 2023

Developing a bispecific anti-ROR1 Antibody Drug Conjugate for hematological and solid tumor treatment

Receptor tyrosine kinase ROR1 is a type I transmembrane protein belongs to the ROR family members. ROR1 is a receptor for Wnt family signaling molecules Wnt5a and is a key regulator of normal cellular process, including cell proliferation, survival, and migration. It is also involved in the development and progression of many types of cancer. Although being an oncofetal protein with limited expression in most of the normal tissues, ROR1 is expressed abnormally in various hematological and solid cancers, making it a highly attractive target for antibody-drug conjugate (ADC) therapy. The current clinical results of ROR1 ADC have been promising in treating patients with relapsed and/or refractory (R/R) hematologic malignancies.

Utilizing our unique and innovated linker platform, we screened many anti-ROR1 ADCs, with defined DAR=4. Those unique ADCs consist of a humanized monoclonal antibody (mAb against single epitope) or a bispecific antibody (BsAb against two epitopes), stably conjugated to an antimitotic agent. The bispecific mAbs that target to two different epitopes of ROR1, are superior to those antibodies that target to single epitope in the binding to ROR1-expressing tumor cells, the induction of tumor cell death and anti-tumor immunity. Our novel linker structure prevents payloads from coming off of the antibody during the circulation, significantly reduced the off-target toxicity. In vitro and In vivo studies demonstrated the antitumor activity of anti-ROR1 ADCs outperformed the lead anti-ROR1 ADC currently in phase II/IIl trial, providing a promising treatment for hematological and solid cancers with a better safety profile and a larger therapeutic window. The lead candidate molecule, BR111A will start the preclinical studies soon.

Citation Format: Xiaobei Zhao, Jie Zhu, Zhenhua Wu, Jing Li, yaqiong zhou, Lei Nie, Gang Chen. Developing a bispecific anti-ROR1 antibody drug conjugate for hematological and solid tumor treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB218.
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 I. , Bakarou Kamate , 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: April 2023

The low overall survival rates of patients with breast cancer in sub-Saharan Africa (SSA) are driven by regionally differing tumor biology, advanced tumor stages at diagnosis, and limited access to therapy. However, it is not known whether regional differences in the composition of the tumor microenvironment (TME) exist and affect patients’ prognosis. In this international, multicentre cohort study, 1,237 formalin-fixed, paraffin-embedded breast cancer samples, including samples of the “African Breast Cancer-Disparities in Outcomes (ABC-DO) Study,” were analyzed. The immune cell phenotypes, their spatial distribution in the TME, and immune escape mechanisms of breast cancer samples from SSA and Germany (n = 117) were investigated using histomorphology, conventional and multiplex IHC, and RNA expression analysis. The data revealed no regional differences in the number of tumor-infiltrating lymphocytes (TIL) in the 1,237 SSA breast cancer samples, while the distribution of TILs in different breast cancer IHC subtypes showed regional diversity, particularly when compared with German samples. Higher TIL densities were associated with better survival in the SSA cohort (n = 400), but regional differences concerning the predictive value of TILs existed. High numbers of CD163+ macrophages and CD3+CD8+ T cells accompanied by reduced cytotoxicity, altered IL10 and IFNγ levels and downregulation of MHC class I components were predominantly detected in breast cancer samples from Western SSA. Features of nonimmunogenic breast cancer phenotypes were associated with reduced patient survival (n = 131). We therefore conclude that regional diversity in the distribution of breast cancer subtypes, TME composition, and immune escape mechanisms should be considered for therapy decisions in SSA and the design of personalized therapies.

See related Spotlight by Bergin et al., p. 705
Table S1 from IOA-244 is a Non–ATP-competitive, Highly Selective, Tolerable PI3K Delta Inhibitor That Targets Solid Tumors and Breaks Immune Tolerance
Authors: Johnson Zoë , Tarantelli Chiara , Civanelli Elisa , Cascione Luciano , Spriano Filippo , Fraser Amy , Shah Pritom , Nomanbhoy Tyzoon , Napoli Sara , Rinaldi Andrea , Niewola-Staszkowska Karolina , Lahn Michael , Perrin Dominique , Wenes Mathias , Migliorini Denis , Bertoni Francesco , van der Veen Lars , Di Conza Giusy
Published: April 2023

Table summarizing the IC50 values derived from previous published experiments performed with IOA-244
Figure S2 from IOA-244 is a Non–ATP-competitive, Highly Selective, Tolerable PI3K Delta Inhibitor That Targets Solid Tumors and Breaks Immune Tolerance
Authors: Johnson Zoë , Tarantelli Chiara , Civanelli Elisa , Cascione Luciano , Spriano Filippo , Fraser Amy , Shah Pritom , Nomanbhoy Tyzoon , Napoli Sara , Rinaldi Andrea , Niewola-Staszkowska Karolina , Lahn Michael , Perrin Dominique , Wenes Mathias , Migliorini Denis , Bertoni Francesco , van der Veen Lars , Di Conza Giusy
Published: April 2023

Target engagement kinase tree