bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplementary Methods S1 from Associations between AI-Assisted Tumor Amphiregulin and Epiregulin IHC and Outcomes from Anti-EGFR Therapy in the Routine Management of Metastatic Colorectal Cancer
Authors: Williams Christopher J.M. , Elliott Faye , Sapanara Nancy , Aghaei Faranak , Zhang Liping , Muranyi Andrea , Yan Dongyao , Bai Isaac , Zhao Zuo , Shires Michael , Wood Henry M. , Richman Susan D. , Hemmings Gemma , Hale Michael , Bottomley Daniel , Galvin Leanne , Cartlidge Caroline , Dance Sarah , Bacon Chris M. , Mansfield Laura , Young-Zvandasara Kathe , Sudan Ajay , Lambert Katy , Bibby Irena , Coupland Sarah E. , Montazeri Amir , Kipling Natalie , Hughes Kathryn , Cross Simon S. , Dewdney Alice , Pheasey Leanne , Leng Cathryn , Gochera Tatenda , Mangham D. Chas , Saunders Mark , Pritchard Martin , Stott Helen , Mukherjee Abhik , Ilyas Mohammad , Silverman Rafael , Hyland Georgina , Sculthorpe Declan , Thornton Kirsty , Gould Imogen , O'Callaghan Ann , Brown Nicholas , Turnbull Samantha , Shaw Lisa , Seymour Matthew T. , West Nicholas P. , Seligmann Jenny F. , Singh Shalini , Shanmugam Kandavel , Quirke Philip
Published: October 2023

Supplementary methods
Supplementary Table S14 from Single-Cell RNA Analysis Reveals Cell-Intrinsic Functions of CAR T Cells Correlating with Response in a Phase II Study of Lymphoma Patients
Authors: Sarén Tina , Ramachandran Mohanraj , Gammelgård Gustav , Lövgren Tanja , Mirabello Claudio , Björklund Åsa K. , Wikström Kristina , Hashemi Jamileh , Freyhult Eva , Ahlström Håkan , Amini Rose-Marie , Hagberg Hans , Loskog Angelica , Enblad Gunilla , Essand Magnus
Published: October 2023

Clinical summary
Supplementary Figure S2 from Associations between AI-Assisted Tumor Amphiregulin and Epiregulin IHC and Outcomes from Anti-EGFR Therapy in the Routine Management of Metastatic Colorectal Cancer
Authors: Williams Christopher J.M. , Elliott Faye , Sapanara Nancy , Aghaei Faranak , Zhang Liping , Muranyi Andrea , Yan Dongyao , Bai Isaac , Zhao Zuo , Shires Michael , Wood Henry M. , Richman Susan D. , Hemmings Gemma , Hale Michael , Bottomley Daniel , Galvin Leanne , Cartlidge Caroline , Dance Sarah , Bacon Chris M. , Mansfield Laura , Young-Zvandasara Kathe , Sudan Ajay , Lambert Katy , Bibby Irena , Coupland Sarah E. , Montazeri Amir , Kipling Natalie , Hughes Kathryn , Cross Simon S. , Dewdney Alice , Pheasey Leanne , Leng Cathryn , Gochera Tatenda , Mangham D. Chas , Saunders Mark , Pritchard Martin , Stott Helen , Mukherjee Abhik , Ilyas Mohammad , Silverman Rafael , Hyland Georgina , Sculthorpe Declan , Thornton Kirsty , Gould Imogen , O'Callaghan Ann , Brown Nicholas , Turnbull Samantha , Shaw Lisa , Seymour Matthew T. , West Nicholas P. , Seligmann Jenny F. , Singh Shalini , Shanmugam Kandavel , Quirke Philip
Published: October 2023

Study flow diagram
Supplementary Table S10 from Single-Cell RNA Analysis Reveals Cell-Intrinsic Functions of CAR T Cells Correlating with Response in a Phase II Study of Lymphoma Patients
Authors: Sarén Tina , Ramachandran Mohanraj , Gammelgård Gustav , Lövgren Tanja , Mirabello Claudio , Björklund Åsa K. , Wikström Kristina , Hashemi Jamileh , Freyhult Eva , Ahlström Håkan , Amini Rose-Marie , Hagberg Hans , Loskog Angelica , Enblad Gunilla , Essand Magnus
Published: October 2023

Proteomics analysis of plasma before CAR-T infusion in relation to CRS
Supplementary Table S9 from Baseline Mutations and ctDNA Dynamics as Prognostic and Predictive Factors in ER-Positive/HER2-Negative Metastatic Breast Cancer Patients
Authors: Pascual Javier , Gil-Gil Miguel , Proszek Paula , Zielinski Christoph , Reay Alistair , Ruiz-Borrego Manuel , Cutts Rosalind , Ciruelos Gil Eva M. , Feber Andrew , Muñoz-Mateu Montserrat , Swift Claire , Bermejo Begoña , Herranz Jesus , Margeli Vila Mireia , Antón Antonio , Kahan Zsuzsanna , Csöszi Tibor , Liu Yuan , Fernandez-Garcia Daniel , Garcia-Murillas Isaac , Hubank Michael , Turner Nicholas C. , Martín Miguel
Published: October 2023

Supplementary Table 9. Summary of PFS results for ESR1 and PIK3CA mutations. Cox regression univariate and multivariate analysis.
Supplementary Table S8 from Baseline Mutations and ctDNA Dynamics as Prognostic and Predictive Factors in ER-Positive/HER2-Negative Metastatic Breast Cancer Patients
Authors: Pascual Javier , Gil-Gil Miguel , Proszek Paula , Zielinski Christoph , Reay Alistair , Ruiz-Borrego Manuel , Cutts Rosalind , Ciruelos Gil Eva M. , Feber Andrew , Muñoz-Mateu Montserrat , Swift Claire , Bermejo Begoña , Herranz Jesus , Margeli Vila Mireia , Antón Antonio , Kahan Zsuzsanna , Csöszi Tibor , Liu Yuan , Fernandez-Garcia Daniel , Garcia-Murillas Isaac , Hubank Michael , Turner Nicholas C. , Martín Miguel
Published: October 2023

Supplementary Table 8. Summary of baseline ESR1 and PIK3CA mutations, with number of affected patients and mean VAF.
Supplementary Table S7 from Baseline Mutations and ctDNA Dynamics as Prognostic and Predictive Factors in ER-Positive/HER2-Negative Metastatic Breast Cancer Patients
Authors: Pascual Javier , Gil-Gil Miguel , Proszek Paula , Zielinski Christoph , Reay Alistair , Ruiz-Borrego Manuel , Cutts Rosalind , Ciruelos Gil Eva M. , Feber Andrew , Muñoz-Mateu Montserrat , Swift Claire , Bermejo Begoña , Herranz Jesus , Margeli Vila Mireia , Antón Antonio , Kahan Zsuzsanna , Csöszi Tibor , Liu Yuan , Fernandez-Garcia Daniel , Garcia-Murillas Isaac , Hubank Michael , Turner Nicholas C. , Martín Miguel
Published: October 2023

Supplementary Table 7. Baseline genomic landscape of mutations distribution in population, by number of mutations or presence/absence, across treatment arms.
Supplementary Table S5 from Baseline Mutations and ctDNA Dynamics as Prognostic and Predictive Factors in ER-Positive/HER2-Negative Metastatic Breast Cancer Patients
Authors: Pascual Javier , Gil-Gil Miguel , Proszek Paula , Zielinski Christoph , Reay Alistair , Ruiz-Borrego Manuel , Cutts Rosalind , Ciruelos Gil Eva M. , Feber Andrew , Muñoz-Mateu Montserrat , Swift Claire , Bermejo Begoña , Herranz Jesus , Margeli Vila Mireia , Antón Antonio , Kahan Zsuzsanna , Csöszi Tibor , Liu Yuan , Fernandez-Garcia Daniel , Garcia-Murillas Isaac , Hubank Michael , Turner Nicholas C. , Martín Miguel
Published: October 2023

Supplementary Table 5. Baseline characteristics comparison between treatment arms in the selected study population
Supplementary Figure S3 from Single-Cell RNA Analysis Reveals Cell-Intrinsic Functions of CAR T Cells Correlating with Response in a Phase II Study of Lymphoma Patients
Authors: Sarén Tina , Ramachandran Mohanraj , Gammelgård Gustav , Lövgren Tanja , Mirabello Claudio , Björklund Åsa K. , Wikström Kristina , Hashemi Jamileh , Freyhult Eva , Ahlström Håkan , Amini Rose-Marie , Hagberg Hans , Loskog Angelica , Enblad Gunilla , Essand Magnus
Published: October 2023

Supplementary Figure S3. Responding patients had a better OS and PFS compared to nonresponding patients.
Supplementary Table S2 from Baseline Mutations and ctDNA Dynamics as Prognostic and Predictive Factors in ER-Positive/HER2-Negative Metastatic Breast Cancer Patients
Authors: Pascual Javier , Gil-Gil Miguel , Proszek Paula , Zielinski Christoph , Reay Alistair , Ruiz-Borrego Manuel , Cutts Rosalind , Ciruelos Gil Eva M. , Feber Andrew , Muñoz-Mateu Montserrat , Swift Claire , Bermejo Begoña , Herranz Jesus , Margeli Vila Mireia , Antón Antonio , Kahan Zsuzsanna , Csöszi Tibor , Liu Yuan , Fernandez-Garcia Daniel , Garcia-Murillas Isaac , Hubank Michael , Turner Nicholas C. , Martín Miguel
Published: October 2023

Supplementary Table 2. Complete table results for all patients (n=201) involved in baseline (C1D1) analysis.
Supplementary Figure S12 from Single-Cell RNA Analysis Reveals Cell-Intrinsic Functions of CAR T Cells Correlating with Response in a Phase II Study of Lymphoma Patients
Authors: Sarén Tina , Ramachandran Mohanraj , Gammelgård Gustav , Lövgren Tanja , Mirabello Claudio , Björklund Åsa K. , Wikström Kristina , Hashemi Jamileh , Freyhult Eva , Ahlström Håkan , Amini Rose-Marie , Hagberg Hans , Loskog Angelica , Enblad Gunilla , Essand Magnus
Published: October 2023

Supplementary Figure S12. Single-cell polyfunctionality in CD4+ CAR-Ts
Supplementary Table S11 from Baseline Mutations and ctDNA Dynamics as Prognostic and Predictive Factors in ER-Positive/HER2-Negative Metastatic Breast Cancer Patients
Authors: Pascual Javier , Gil-Gil Miguel , Proszek Paula , Zielinski Christoph , Reay Alistair , Ruiz-Borrego Manuel , Cutts Rosalind , Ciruelos Gil Eva M. , Feber Andrew , Muñoz-Mateu Montserrat , Swift Claire , Bermejo Begoña , Herranz Jesus , Margeli Vila Mireia , Antón Antonio , Kahan Zsuzsanna , Csöszi Tibor , Liu Yuan , Fernandez-Garcia Daniel , Garcia-Murillas Isaac , Hubank Michael , Turner Nicholas C. , Martín Miguel
Published: October 2023

Supplementary Table 11. Baseline characteristics comparison between population with CDR calculation (n=120) vs non-CDR population (n=81).
Supplementary Figure S10 from Single-Cell RNA Analysis Reveals Cell-Intrinsic Functions of CAR T Cells Correlating with Response in a Phase II Study of Lymphoma Patients
Authors: Sarén Tina , Ramachandran Mohanraj , Gammelgård Gustav , Lövgren Tanja , Mirabello Claudio , Björklund Åsa K. , Wikström Kristina , Hashemi Jamileh , Freyhult Eva , Ahlström Håkan , Amini Rose-Marie , Hagberg Hans , Loskog Angelica , Enblad Gunilla , Essand Magnus
Published: October 2023

Supplementary Figure S10. A) Overview of the CAR-T production process. B) Expansion of the
CAR-T product over time for responders (R; n=9) and non-responders (NR; n=15) during ex
vivo CAR-T manufacturing. Values are shown as mean ± SEM. Two-way ANOVA with
Sidak’s correction for multiple comparison was used to compare between groups. C) Days of
ex vivo culture during CAR-T manufacturing from R (n=9) and NR (n=15). Each dot
represent data from one patient and values are shown as mean ± SEM. Unpaired t-test was
used to compare between groups. D) Correlation between the highest CAR copy number
(peak CAR copies) detected in patient blood upon CAR-T infusion and days of ex-vivo CART expansion during manufacturing. Each dot represent data from one patient. E) Correlation
between the highest CAR copy number (peak CAR copies) detected in patient blood upon
CAR-T infusion and fold ex vivo expansion. F) Schematic illustration describing the analysis
of how genes upregulated in non-responding patients (NR) change in expression (up- or
down-regulated) with culture time. G) Genes with negative (downregulated) and positive
(upregulated) correlation with culture time were compared with the genes specifically
upregulated in CD8+
CAR-Ts from non-responding patients.
Supplementary Figure S5 from Baseline Mutations and ctDNA Dynamics as Prognostic and Predictive Factors in ER-Positive/HER2-Negative Metastatic Breast Cancer Patients
Authors: Pascual Javier , Gil-Gil Miguel , Proszek Paula , Zielinski Christoph , Reay Alistair , Ruiz-Borrego Manuel , Cutts Rosalind , Ciruelos Gil Eva M. , Feber Andrew , Muñoz-Mateu Montserrat , Swift Claire , Bermejo Begoña , Herranz Jesus , Margeli Vila Mireia , Antón Antonio , Kahan Zsuzsanna , Csöszi Tibor , Liu Yuan , Fernandez-Garcia Daniel , Garcia-Murillas Isaac , Hubank Michael , Turner Nicholas C. , Martín Miguel
Published: October 2023

Supplementary Figure 5. CDR and clinical benefit rate within the longitudinal predictive ctDNA analysis.
Supplementary Figure S3 from Baseline Mutations and ctDNA Dynamics as Prognostic and Predictive Factors in ER-Positive/HER2-Negative Metastatic Breast Cancer Patients
Authors: Pascual Javier , Gil-Gil Miguel , Proszek Paula , Zielinski Christoph , Reay Alistair , Ruiz-Borrego Manuel , Cutts Rosalind , Ciruelos Gil Eva M. , Feber Andrew , Muñoz-Mateu Montserrat , Swift Claire , Bermejo Begoña , Herranz Jesus , Margeli Vila Mireia , Antón Antonio , Kahan Zsuzsanna , Csöszi Tibor , Liu Yuan , Fernandez-Garcia Daniel , Garcia-Murillas Isaac , Hubank Michael , Turner Nicholas C. , Martín Miguel
Published: October 2023

Supplementary Figure 3. Survival analysis in baseline population (C1D1) on TP53 mutations, within the population with any detectable mutation (n=146).
Supplementary Figure S2 from Baseline Mutations and ctDNA Dynamics as Prognostic and Predictive Factors in ER-Positive/HER2-Negative Metastatic Breast Cancer Patients
Authors: Pascual Javier , Gil-Gil Miguel , Proszek Paula , Zielinski Christoph , Reay Alistair , Ruiz-Borrego Manuel , Cutts Rosalind , Ciruelos Gil Eva M. , Feber Andrew , Muñoz-Mateu Montserrat , Swift Claire , Bermejo Begoña , Herranz Jesus , Margeli Vila Mireia , Antón Antonio , Kahan Zsuzsanna , Csöszi Tibor , Liu Yuan , Fernandez-Garcia Daniel , Garcia-Murillas Isaac , Hubank Michael , Turner Nicholas C. , Martín Miguel
Published: October 2023

Supplementary Figure 2. PFS analysis in baseline population (C1D1) on TP53 mutations, by treatment arms.
Supplementary Table S3 from Integrated Genomic and Transcriptomic Analysis Improves Disease Classification and Risk Stratification of MDS with Ring Sideroblasts
Authors: Todisco Gabriele , Creignou Maria , Bernard Elsa , Björklund Ann-Charlotte , Moura Pedro Luis , Tesi Bianca , Mortera-Blanco Teresa , Sander Birgitta , Jansson Monika , Walldin Gunilla , Barbosa Indira , Reinsbach Susanne E. , Hofman Isabel Juliana , Nilsson Christer , Yoshizato Tetsuichi , Dimitriou Marios , Chang David , Olafsdottir Svannildur , Venckute Larsson Sigita , Tobiasson Magnus , Malcovati Luca , Woll Petter , Jacobsen Sten Eirik W. , Papaemmanuil Elli , Hellström-Lindberg Eva
Published: October 2023

List of differentially expressed genes associated with EMK, INT and IMP profile.
Supplementary Table S2 from Integrated Genomic and Transcriptomic Analysis Improves Disease Classification and Risk Stratification of MDS with Ring Sideroblasts
Authors: Todisco Gabriele , Creignou Maria , Bernard Elsa , Björklund Ann-Charlotte , Moura Pedro Luis , Tesi Bianca , Mortera-Blanco Teresa , Sander Birgitta , Jansson Monika , Walldin Gunilla , Barbosa Indira , Reinsbach Susanne E. , Hofman Isabel Juliana , Nilsson Christer , Yoshizato Tetsuichi , Dimitriou Marios , Chang David , Olafsdottir Svannildur , Venckute Larsson Sigita , Tobiasson Magnus , Malcovati Luca , Woll Petter , Jacobsen Sten Eirik W. , Papaemmanuil Elli , Hellström-Lindberg Eva
Published: October 2023

Demographic and clinical features of cases and controls included into the study.
Supplementary Results S1 from Integrated Genomic and Transcriptomic Analysis Improves Disease Classification and Risk Stratification of MDS with Ring Sideroblasts
Authors: Todisco Gabriele , Creignou Maria , Bernard Elsa , Björklund Ann-Charlotte , Moura Pedro Luis , Tesi Bianca , Mortera-Blanco Teresa , Sander Birgitta , Jansson Monika , Walldin Gunilla , Barbosa Indira , Reinsbach Susanne E. , Hofman Isabel Juliana , Nilsson Christer , Yoshizato Tetsuichi , Dimitriou Marios , Chang David , Olafsdottir Svannildur , Venckute Larsson Sigita , Tobiasson Magnus , Malcovati Luca , Woll Petter , Jacobsen Sten Eirik W. , Papaemmanuil Elli , Hellström-Lindberg Eva
Published: October 2023

Supplementary Results
Supplementary Figure S9 from Integrated Genomic and Transcriptomic Analysis Improves Disease Classification and Risk Stratification of MDS with Ring Sideroblasts
Authors: Todisco Gabriele , Creignou Maria , Bernard Elsa , Björklund Ann-Charlotte , Moura Pedro Luis , Tesi Bianca , Mortera-Blanco Teresa , Sander Birgitta , Jansson Monika , Walldin Gunilla , Barbosa Indira , Reinsbach Susanne E. , Hofman Isabel Juliana , Nilsson Christer , Yoshizato Tetsuichi , Dimitriou Marios , Chang David , Olafsdottir Svannildur , Venckute Larsson Sigita , Tobiasson Magnus , Malcovati Luca , Woll Petter , Jacobsen Sten Eirik W. , Papaemmanuil Elli , Hellström-Lindberg Eva
Published: October 2023

Item consensus for K=3 showing stable item-consensus values across the whole cohort.
Supplementary Data 2 from Diagnostic Performance of a Tumor Marker Gene Test to Personalize Serum CA19–9 Reference Ranges
Authors: Dbouk Mohamad , Abe Toshiya , Koi Chiho , Ando Yohei , Saba Helena , Abou Diwan Elizabeth , MacGregor-Das Anne , Blackford Amanda L. , Mocci Evelina , Beierl Katie , Dbouk Ali , He Jin , Burkhart Richard , Lennon Anne Marie , Sokoll Lori , Canto Marcia Irene , Eshleman James R. , Goggins Michael
Published: October 2023

Supplementary Figure 2
Supplementary Figure S6 from Integrated Genomic and Transcriptomic Analysis Improves Disease Classification and Risk Stratification of MDS with Ring Sideroblasts
Authors: Todisco Gabriele , Creignou Maria , Bernard Elsa , Björklund Ann-Charlotte , Moura Pedro Luis , Tesi Bianca , Mortera-Blanco Teresa , Sander Birgitta , Jansson Monika , Walldin Gunilla , Barbosa Indira , Reinsbach Susanne E. , Hofman Isabel Juliana , Nilsson Christer , Yoshizato Tetsuichi , Dimitriou Marios , Chang David , Olafsdottir Svannildur , Venckute Larsson Sigita , Tobiasson Magnus , Malcovati Luca , Woll Petter , Jacobsen Sten Eirik W. , Papaemmanuil Elli , Hellström-Lindberg Eva
Published: October 2023

– Results from Gene Ontology enrichment analysis (molecular function dataset) for the top 250 contributors of principal component 1 (PC1)
Supplementary Figure S4 from Integrated Genomic and Transcriptomic Analysis Improves Disease Classification and Risk Stratification of MDS with Ring Sideroblasts
Authors: Todisco Gabriele , Creignou Maria , Bernard Elsa , Björklund Ann-Charlotte , Moura Pedro Luis , Tesi Bianca , Mortera-Blanco Teresa , Sander Birgitta , Jansson Monika , Walldin Gunilla , Barbosa Indira , Reinsbach Susanne E. , Hofman Isabel Juliana , Nilsson Christer , Yoshizato Tetsuichi , Dimitriou Marios , Chang David , Olafsdottir Svannildur , Venckute Larsson Sigita , Tobiasson Magnus , Malcovati Luca , Woll Petter , Jacobsen Sten Eirik W. , Papaemmanuil Elli , Hellström-Lindberg Eva
Published: October 2023

UMAP plot of MDSRS+ bone marrow CD34 mononuclear cells transcriptomes. Each point is one patient, overlaid with results from unsupervised clustering.
Supplementary Figure S20 from Integrated Genomic and Transcriptomic Analysis Improves Disease Classification and Risk Stratification of MDS with Ring Sideroblasts
Authors: Todisco Gabriele , Creignou Maria , Bernard Elsa , Björklund Ann-Charlotte , Moura Pedro Luis , Tesi Bianca , Mortera-Blanco Teresa , Sander Birgitta , Jansson Monika , Walldin Gunilla , Barbosa Indira , Reinsbach Susanne E. , Hofman Isabel Juliana , Nilsson Christer , Yoshizato Tetsuichi , Dimitriou Marios , Chang David , Olafsdottir Svannildur , Venckute Larsson Sigita , Tobiasson Magnus , Malcovati Luca , Woll Petter , Jacobsen Sten Eirik W. , Papaemmanuil Elli , Hellström-Lindberg Eva
Published: October 2023

MDSRS+ event free survival (EFS) stratified by estimated MEP percentage in the four genetic subgroups (A-D).
Supplementary Figure S2 from Integrated Genomic and Transcriptomic Analysis Improves Disease Classification and Risk Stratification of MDS with Ring Sideroblasts
Authors: Todisco Gabriele , Creignou Maria , Bernard Elsa , Björklund Ann-Charlotte , Moura Pedro Luis , Tesi Bianca , Mortera-Blanco Teresa , Sander Birgitta , Jansson Monika , Walldin Gunilla , Barbosa Indira , Reinsbach Susanne E. , Hofman Isabel Juliana , Nilsson Christer , Yoshizato Tetsuichi , Dimitriou Marios , Chang David , Olafsdottir Svannildur , Venckute Larsson Sigita , Tobiasson Magnus , Malcovati Luca , Woll Petter , Jacobsen Sten Eirik W. , Papaemmanuil Elli , Hellström-Lindberg Eva
Published: October 2023

Clonal hierarchy analysis of SF3B1-SRSF2 co-mutated cases. A. Results from the hierarchical rank analysis of mutations detected by DNAseq in the 4 cases harboring both SF3B1 and SRSF2 mutation using Pyclone. The analysis was also performed using DPClust, which provided converging results (data not shown). Tumor cell fraction (axes) for each detected clone and its 95% confidence interval (dot size) is represented in a scatter-plot, using different color according to the cluster driving mutation (SF3B1, red; SRSF2, blue; other drivers, gray). SF3B1 dominancy in MDS392 and MDS 640, together with the SRSF2 large clone size are suggestive of both splicing factor mutations in the same clone. On the contrary, MDS694 and MDS965 had a dominant SF3B1 clone associated with a very little and probably independent SRSF2 secondary clone. B. Results from single-cell derived colony-forming unit (CFU) genotyping confirming the concurrent double splicing factor mutations within the same clone in patient MDS382 and MDS640. CFU experiment was not carried out for the other two cases because of the very low probability of SF3B1/SRSF2 double positive clone identification, as already suggested by current data in the literature related to the presence of SF3B1K700E mutation (ref. 1).
Supplementary Table S4 from Neoantigen Targetability in Progressive Advanced Melanoma
Authors: van den Bulk Jitske , Verdegaal Els M.E. , van der Ploeg Manon , Visser Marten , Nunes Joana B. , de Ru Arnoud H. , Tjokrodirijo Rayman T.N. , Ijsselsteijn Marieke E. , Janssen Natasja I. , van der Breggen Ruud , de Bruin Linda , de Kok Pita , Janssen George M.C. , Ruano Dina , Kapiteijn Ellen H.W. , van Veelen Peter A. , de Miranda Noel F.C.C. , van der Burg Sjoerd H.
Published: October 2023

Tumor-associated antigen peptide sequences assessed for elution.
Supplementary Table S3 from Neoantigen Targetability in Progressive Advanced Melanoma
Authors: van den Bulk Jitske , Verdegaal Els M.E. , van der Ploeg Manon , Visser Marten , Nunes Joana B. , de Ru Arnoud H. , Tjokrodirijo Rayman T.N. , Ijsselsteijn Marieke E. , Janssen Natasja I. , van der Breggen Ruud , de Bruin Linda , de Kok Pita , Janssen George M.C. , Ruano Dina , Kapiteijn Ellen H.W. , van Veelen Peter A. , de Miranda Noel F.C.C. , van der Burg Sjoerd H.
Published: October 2023

HLA class I genotypes as determined by exome and transcriptome sequencing.
Supplementary Figure S16 from Integrated Genomic and Transcriptomic Analysis Improves Disease Classification and Risk Stratification of MDS with Ring Sideroblasts
Authors: Todisco Gabriele , Creignou Maria , Bernard Elsa , Björklund Ann-Charlotte , Moura Pedro Luis , Tesi Bianca , Mortera-Blanco Teresa , Sander Birgitta , Jansson Monika , Walldin Gunilla , Barbosa Indira , Reinsbach Susanne E. , Hofman Isabel Juliana , Nilsson Christer , Yoshizato Tetsuichi , Dimitriou Marios , Chang David , Olafsdottir Svannildur , Venckute Larsson Sigita , Tobiasson Magnus , Malcovati Luca , Woll Petter , Jacobsen Sten Eirik W. , Papaemmanuil Elli , Hellström-Lindberg Eva
Published: October 2023

EMK and IMP signature validation on HSPC sorted populations. Differential gene expression analysis across MDSRS+ with EMK profile, MDSRS- with IMP profile and NBM (3 cases each) according to Lin marker expression. Differential expressed genes (row) between EMK and IMP groups were selected. Each row represents a gene, and each column represents a sample. Design comparison (case) and sorted population (condition) are shown as covariates.
Supplementary Figure S5 from Neoantigen Targetability in Progressive Advanced Melanoma
Authors: van den Bulk Jitske , Verdegaal Els M.E. , van der Ploeg Manon , Visser Marten , Nunes Joana B. , de Ru Arnoud H. , Tjokrodirijo Rayman T.N. , Ijsselsteijn Marieke E. , Janssen Natasja I. , van der Breggen Ruud , de Bruin Linda , de Kok Pita , Janssen George M.C. , Ruano Dina , Kapiteijn Ellen H.W. , van Veelen Peter A. , de Miranda Noel F.C.C. , van der Burg Sjoerd H.
Published: October 2023

Putative neoantigens in early and later metastatic lesions.
Supplementary Figure S11 from Integrated Genomic and Transcriptomic Analysis Improves Disease Classification and Risk Stratification of MDS with Ring Sideroblasts
Authors: Todisco Gabriele , Creignou Maria , Bernard Elsa , Björklund Ann-Charlotte , Moura Pedro Luis , Tesi Bianca , Mortera-Blanco Teresa , Sander Birgitta , Jansson Monika , Walldin Gunilla , Barbosa Indira , Reinsbach Susanne E. , Hofman Isabel Juliana , Nilsson Christer , Yoshizato Tetsuichi , Dimitriou Marios , Chang David , Olafsdottir Svannildur , Venckute Larsson Sigita , Tobiasson Magnus , Malcovati Luca , Woll Petter , Jacobsen Sten Eirik W. , Papaemmanuil Elli , Hellström-Lindberg Eva
Published: October 2023

ABCB7 expression throughout the spectrum of MDSRS+ genotypes. ABCB7 downregulation is restricted to SF3B1-mutant MDSRS+.
Supplementary Figure S3 from Neoantigen Targetability in Progressive Advanced Melanoma
Authors: van den Bulk Jitske , Verdegaal Els M.E. , van der Ploeg Manon , Visser Marten , Nunes Joana B. , de Ru Arnoud H. , Tjokrodirijo Rayman T.N. , Ijsselsteijn Marieke E. , Janssen Natasja I. , van der Breggen Ruud , de Bruin Linda , de Kok Pita , Janssen George M.C. , Ruano Dina , Kapiteijn Ellen H.W. , van Veelen Peter A. , de Miranda Noel F.C.C. , van der Burg Sjoerd H.
Published: October 2023

T cell recognition of melanoma cell lines derived from early and later metastatic lesions.
Supplementary Figure S10 from Integrated Genomic and Transcriptomic Analysis Improves Disease Classification and Risk Stratification of MDS with Ring Sideroblasts
Authors: Todisco Gabriele , Creignou Maria , Bernard Elsa , Björklund Ann-Charlotte , Moura Pedro Luis , Tesi Bianca , Mortera-Blanco Teresa , Sander Birgitta , Jansson Monika , Walldin Gunilla , Barbosa Indira , Reinsbach Susanne E. , Hofman Isabel Juliana , Nilsson Christer , Yoshizato Tetsuichi , Dimitriou Marios , Chang David , Olafsdottir Svannildur , Venckute Larsson Sigita , Tobiasson Magnus , Malcovati Luca , Woll Petter , Jacobsen Sten Eirik W. , Papaemmanuil Elli , Hellström-Lindberg Eva
Published: October 2023

Optimal number of clusters defined by average silhouette width method.
Table S2 from HDACi-dependent Microenvironmental Normalization Overcomes Tumor Burden–induced T-cell Exhaustion
Authors: Nguyen Andrew , Brown Dominique , Krishnan Ramya , Bastin Donald , Deng Li , Chen Lan , Salem Omar , Walsh Scott R. , Bramson Jonathan L. , Wan Yonghong
Published: October 2023

Table S2: Overrepresented GO terms associated with Module 2 (M2)
Supplementary Figure S4 from Patient-Specific Targeting of the T-Cell Receptor Variable Region as a Therapeutic Strategy in Clonal T-Cell Diseases
Authors: Lucero Olivia M. , Lee Ji-Ann , Bowman Jenna , Johnson Kara , Sapparapu Gopal , Thomas John K. , Fan Guang , Chang Bill H. , Thiel-Klare Karina , Eide Christopher A. , Okada Craig , Palazzolo Mike , Lind Evan , Kosaka Yoko , Druker Brian J. , Lydon Nicholas , Bowers Peter M.
Published: October 2023

Supplementary Figure 4. Target T-cells do not undergo complement dependent cytotoxicity (CDC).
Supplementary Figure S3 from Patient-Specific Targeting of the T-Cell Receptor Variable Region as a Therapeutic Strategy in Clonal T-Cell Diseases
Authors: Lucero Olivia M. , Lee Ji-Ann , Bowman Jenna , Johnson Kara , Sapparapu Gopal , Thomas John K. , Fan Guang , Chang Bill H. , Thiel-Klare Karina , Eide Christopher A. , Okada Craig , Palazzolo Mike , Lind Evan , Kosaka Yoko , Druker Brian J. , Lydon Nicholas , Bowers Peter M.
Published: October 2023

Supplementary Figure 3: Vβ monoclonal antibodies induce antibody dependent cellular cytotoxicity of target cells.
Figure S3 from HDACi-dependent Microenvironmental Normalization Overcomes Tumor Burden–induced T-cell Exhaustion
Authors: Nguyen Andrew , Brown Dominique , Krishnan Ramya , Bastin Donald , Deng Li , Chen Lan , Salem Omar , Walsh Scott R. , Bramson Jonathan L. , Wan Yonghong
Published: October 2023

Figure S3: CEMiTool module analysis and hub gene identification
Supplementary Tables 1-3 from Efficacy and Safety of Stereotactic Body Radiotherapy Combined with Camrelizumab and Apatinib in Patients with Hepatocellular Carcinoma with Portal Vein Tumor Thrombus
Authors: Hu Yue , Zhou Min , Tang Jing , Li Shuang , Liu Hongli , Hu Jianli , Ma Hong , Liu Junli , Qin Tingting , Yu Xiongjie , Chen Yongshun , Peng Jin , Zou Yanmei , Zhang Tao , Xue Jun
Published: October 2023

Supplementary Tables 1-3
Supplementary Figure S1 from Immune Marker Spatial Distribution and Clinical Outcome after PD-1 Blockade in Mismatch Repair–deficient, Advanced Colorectal Carcinomas
Authors: Saberzadeh-Ardestani Bahar , Graham Rondell P. , McMahon Sara , Ahanonu Eze , Shi Qian , Williams Crystal , Hubbard Antony , Zhang Wenjun , Muranyi Andrea , Yan Dongyao , Jin Zhaohui , Shanmugam Kandavel , Sinicrope Frank A.
Published: October 2023

Supplementary Figure S1. PD-L1 (green) was expressed in (A) CD3+ T lymphocytes (magenta/pink), (B) CD68+ macrophages (red), panCK+ (cyan/light blue) tumor cells, and (C) tumor cells (red). PD-1 expression on CD8+ T lymphocytes was also observed.
Supplementary Table S4 from Anlotinib in Locally Advanced or Metastatic Radioiodine-Refractory Differentiated Thyroid Carcinoma: A Randomized, Double-Blind, Multicenter Phase II Trial
Authors: Chi Yihebali , Zheng Xiangqian , Zhang Yuan , Shi Feng , Cheng Ying , Guo Zhuming , Ge Minghua , Qin Jianwu , Zhang Jiewu , Li Zhendong , Zhou Xiaohong , Huang Rui , Chen Xiaohong , Liu Hui , Cheng Ruochuan , Xu Zhengang , Li Dapeng , Tang Pingzhang , Gao Ming
Published: October 2023

Grade 3 or above treatment-related adverse events (TRAEs)
Supplementary Data 1 from Safety and Tolerability of Low-Dose Radiation and Stereotactic Body Radiotherapy + Sintilimab for Treatment-Naïve Stage IV PD-L1+ Non–Small Cell Lung Cancer Patients
Authors: Zhou Xiaojuan , Zhou Laiyan , Yao Zhuoran , Huang Meijuan , Gong Youling , Zou Bingwen , Zhu Jiang , Liu Yongmei , Peng Feng , Zhang Yan , Yu Min , Li Yanying , Na Feifei , Wu Yijun , Kang Kai , Xiu Weigang , Zhang Xuanwei , Zhou Lin , Xu Yong , Wang Jin , Wang Yan , Yang Xue , Wu Yuanjun , Li Rui , Zhang Yu , Yang Zhenzhou , Zhou Zhipeng , Bai Jing , Yi Xin , Tong Ruizhan , Yin Limei , Chen Chong , Niedermann Gabriele , Lu You , Xue Jianxin
Published: October 2023

2 figures,3 tables and 3 texts
Supplementary Table S1 from Anlotinib in Locally Advanced or Metastatic Radioiodine-Refractory Differentiated Thyroid Carcinoma: A Randomized, Double-Blind, Multicenter Phase II Trial
Authors: Chi Yihebali , Zheng Xiangqian , Zhang Yuan , Shi Feng , Cheng Ying , Guo Zhuming , Ge Minghua , Qin Jianwu , Zhang Jiewu , Li Zhendong , Zhou Xiaohong , Huang Rui , Chen Xiaohong , Liu Hui , Cheng Ruochuan , Xu Zhengang , Li Dapeng , Tang Pingzhang , Gao Ming
Published: October 2023

Representativeness of Study Participants
Supplementary Methods S1 from Anlotinib in Locally Advanced or Metastatic Radioiodine-Refractory Differentiated Thyroid Carcinoma: A Randomized, Double-Blind, Multicenter Phase II Trial
Authors: Chi Yihebali , Zheng Xiangqian , Zhang Yuan , Shi Feng , Cheng Ying , Guo Zhuming , Ge Minghua , Qin Jianwu , Zhang Jiewu , Li Zhendong , Zhou Xiaohong , Huang Rui , Chen Xiaohong , Liu Hui , Cheng Ruochuan , Xu Zhengang , Li Dapeng , Tang Pingzhang , Gao Ming
Published: October 2023

Supplementary methods
Supplementary Figure S5 from Anlotinib in Locally Advanced or Metastatic Radioiodine-Refractory Differentiated Thyroid Carcinoma: A Randomized, Double-Blind, Multicenter Phase II Trial
Authors: Chi Yihebali , Zheng Xiangqian , Zhang Yuan , Shi Feng , Cheng Ying , Guo Zhuming , Ge Minghua , Qin Jianwu , Zhang Jiewu , Li Zhendong , Zhou Xiaohong , Huang Rui , Chen Xiaohong , Liu Hui , Cheng Ruochuan , Xu Zhengang , Li Dapeng , Tang Pingzhang , Gao Ming
Published: October 2023

Best changes in the sum of longest diameters of target lesions for the anlotinib group and the placebo group.
Purplish red: confirmed partial response; blue: stable disease lasting at least 4 week.
Supplementary Table S2 from Axicabtagene Ciloleucel in Combination with the 4–1BB Agonist Utomilumab in Patients with Relapsed/Refractory Large B-Cell Lymphoma: Phase 1 Results from ZUMA-11
Authors: Jain Michael D. , Miklos David B. , Jacobson Caron A. , Timmerman John M. , Sun Jennifer , Nater Jenny , Fang Xiang , Patel Ankit , Davis Madison , Heeke Darren , Trinh Tan , Mattie Mike , Neumann Frank , Kim Jenny J. , To Christina , Filosto Simone , Reshef Ran
Published: October 2023

Peak Concentration and AUC0–29 of Serum Utomilumab
Supplementary Table S1 from Axicabtagene Ciloleucel in Combination with the 4–1BB Agonist Utomilumab in Patients with Relapsed/Refractory Large B-Cell Lymphoma: Phase 1 Results from ZUMA-11
Authors: Jain Michael D. , Miklos David B. , Jacobson Caron A. , Timmerman John M. , Sun Jennifer , Nater Jenny , Fang Xiang , Patel Ankit , Davis Madison , Heeke Darren , Trinh Tan , Mattie Mike , Neumann Frank , Kim Jenny J. , To Christina , Filosto Simone , Reshef Ran
Published: October 2023

Representativeness of Study Participants
Supplementary Figure S8 from Axicabtagene Ciloleucel in Combination with the 4–1BB Agonist Utomilumab in Patients with Relapsed/Refractory Large B-Cell Lymphoma: Phase 1 Results from ZUMA-11
Authors: Jain Michael D. , Miklos David B. , Jacobson Caron A. , Timmerman John M. , Sun Jennifer , Nater Jenny , Fang Xiang , Patel Ankit , Davis Madison , Heeke Darren , Trinh Tan , Mattie Mike , Neumann Frank , Kim Jenny J. , To Christina , Filosto Simone , Reshef Ran
Published: October 2023

CCR7 and CD45RA T-cell Phenotypes After Axi-cel and Utomilumab Infusions
Supplementary Figure S1 from Anlotinib in Locally Advanced or Metastatic Radioiodine-Refractory Differentiated Thyroid Carcinoma: A Randomized, Double-Blind, Multicenter Phase II Trial
Authors: Chi Yihebali , Zheng Xiangqian , Zhang Yuan , Shi Feng , Cheng Ying , Guo Zhuming , Ge Minghua , Qin Jianwu , Zhang Jiewu , Li Zhendong , Zhou Xiaohong , Huang Rui , Chen Xiaohong , Liu Hui , Cheng Ruochuan , Xu Zhengang , Li Dapeng , Tang Pingzhang , Gao Ming
Published: October 2023

(A) Kaplan–Meier estimate of progress-free survival (PFS) in patients who had radiographic progressive disease within 3 months before enrollment. (B) Kaplan–Meier estimate of PFS in patients who had radiographic progressive disease beyond 3 months before enrollment. (C) Kaplan–Meier estimate of PFS in patients who had radiographic progressive disease within 12 months before enrollment. (D) Kaplan–Meier estimate of PFS in patients who had radiographic progressive disease beyond 12 months before enrollment. The tick marks indicate censored data.
Supplementary Figure S2 from Axicabtagene Ciloleucel in Combination with the 4–1BB Agonist Utomilumab in Patients with Relapsed/Refractory Large B-Cell Lymphoma: Phase 1 Results from ZUMA-11
Authors: Jain Michael D. , Miklos David B. , Jacobson Caron A. , Timmerman John M. , Sun Jennifer , Nater Jenny , Fang Xiang , Patel Ankit , Davis Madison , Heeke Darren , Trinh Tan , Mattie Mike , Neumann Frank , Kim Jenny J. , To Christina , Filosto Simone , Reshef Ran
Published: October 2023

CRS and NE Management Algorithms (1)
Supplementary Figure S1 from Axicabtagene Ciloleucel in Combination with the 4–1BB Agonist Utomilumab in Patients with Relapsed/Refractory Large B-Cell Lymphoma: Phase 1 Results from ZUMA-11
Authors: Jain Michael D. , Miklos David B. , Jacobson Caron A. , Timmerman John M. , Sun Jennifer , Nater Jenny , Fang Xiang , Patel Ankit , Davis Madison , Heeke Darren , Trinh Tan , Mattie Mike , Neumann Frank , Kim Jenny J. , To Christina , Filosto Simone , Reshef Ran
Published: October 2023

ZUMA-11 Study Schema
Supplementary Data 1 from Depth of Radiographic Response and Time to Tumor Regrowth Predicts Overall Survival Following Anti-VEGF Therapy in Recurrent Glioblastoma
Authors: Ellingson Benjamin M. , Hagiwara Akifumi , Morris Connor J. , Cho Nicholas S. , Oshima Sonoko , Sanvito Francesco , Oughourlian Talia C. , Telesca Donatello , Raymond Catalina , Abrey Lauren E. , Garcia Josep , Aftab Dana T. , Hessel Colin , Rachmilewitz Minei Tamar , Harats Dror , Nathanson David A. , Wen Patrick Y. , Cloughesy Timothy F.
Published: October 2023

Supplemental Tables S1-S5
Supplementary Table S2 from Safety, Immunologic, and Clinical Activity of Durvalumab in Combination with Olaparib or Cediranib in Advanced Leiomyosarcoma: Results of the DAPPER Clinical Trial.
Authors: Salawu Abdulazeez , Wang Ben X. , Han Ming , Geady Caryn , Heirali Alya , Berman Hal K. , Pfister Thomas D. , Hernando-Calvo Alberto , Al-Ezzi Esmail Mutahar , Stayner Lee-Anne , Gupta Abha A. , Ayodele Olubukola , Lam Bernard , Hansen Aaron R. , Spreafico Anna , Bedard Philippe L. , Butler Marcus O. , Avery Lisa , Coburn Bryan , Haibe-Kains Benjamin , Siu Lillian L. , Abdul Razak Albiruni R.
Published: October 2023

Table S2: Best overall responses (iRECIST) of leiomyosarcoma patients on the DAPPER study
Supplementary Table S1 from Safety, Immunologic, and Clinical Activity of Durvalumab in Combination with Olaparib or Cediranib in Advanced Leiomyosarcoma: Results of the DAPPER Clinical Trial.
Authors: Salawu Abdulazeez , Wang Ben X. , Han Ming , Geady Caryn , Heirali Alya , Berman Hal K. , Pfister Thomas D. , Hernando-Calvo Alberto , Al-Ezzi Esmail Mutahar , Stayner Lee-Anne , Gupta Abha A. , Ayodele Olubukola , Lam Bernard , Hansen Aaron R. , Spreafico Anna , Bedard Philippe L. , Butler Marcus O. , Avery Lisa , Coburn Bryan , Haibe-Kains Benjamin , Siu Lillian L. , Abdul Razak Albiruni R.
Published: October 2023

Table S1: Best overall response (RECIST v1.1) of leiomyosarcoma patients on the DAPPER
study
Supplementary Figure S2 from Targeting Hedgehog Signaling with Glasdegib in Patients with Refractory Sclerotic Chronic GVHD: A Report of Two Phase I/II Trials
Authors: Rodríguez-Arbolí Eduardo , Lee Catherine J. , Caballero-Velázquez Teresa , Martínez Carmen , García-Calderón Clara , Jiménez-León María Reyes , Bermúdez-Rodríguez María Aránzazu , López-Corral Lucía , Triguero Ana , Onstad Lynn , Horwitz Mitchell E. , Sarantopoulos Stefanie , Lee Stephanie J. , Pérez-Simón José Antonio
Published: October 2023

Phosphoflow analysis of T-cell activation signaling pathways. Flow cytometric measurements of ERK (pT202/204), p38 (pT180/y182), STAT3 (pY705), and STAT5 (pY694) phosphorylation were performed at baseline and after activation with PMA 40 nM (pERK and p38 analyses), IL-2 50 ng/mL (pSTAT5 analysis) or IL-6 20 ng/mL (pSTAT3 analysis) in the CD4+ and CD8+ T-cell subsets. Differences between post-activation/resting MFI ratios were examined in skin/joints scGVHD responder (C1D1: n=13; C2D1: n=13; C4D1: n=12) and non-responder (C1D1: n=7; C2D1: n=7; C4D1: n=5) patients in serial evaluations on day 1 of cycles 1, 2 and 4. MFI, median fluorescence intensity; n.s., non-statistically significant. *Omnibus Friedman test. No differences were detected in post-hoc tests.
Data from A Population of Tumor-Infiltrating CD4+ T Cells Co-Expressing CD38 and CD39 Is Associated with Checkpoint Inhibitor Resistance
Authors: Mitra Ankita , Thompson Brian , Strange Ann , Amato Carol M. , Vassallo Melinda , Dolgalev Igor , Hester-McCullough Jonathan , Muramatsu Tomoaki , Kimono Diana , Puranik Amrutesh S. , Weber Jeffrey S. , Woods David
Published: October 2023

AbstractPurpose:
We previously showed that elevated frequencies of peripheral blood CD3+CD4+CD127−GARP−CD38+CD39+ T cells were associated with checkpoint immunotherapy resistance in patients with metastatic melanoma. In the present study, we sought to further investigate this population of ectoenzyme-expressing T cells (Teee).
Experimental Design:
Teee derived from the peripheral blood of patients with metastatic melanoma were evaluated by bulk RNA-sequencing (RNA-seq) and flow cytometry. The presence of Teee in the tumor microenvironment was assessed using publically available single-cell RNA-seq datasets of melanoma, lung, and bladder cancers along with multispectral immunofluorescent imaging of melanoma patient formalin-fixed, paraffin-embedded specimens. Suppressive function of Teee was determined by an in vitro autologous suppression assay.
Results:
Teee had phenotypes associated with proliferation, apoptosis, exhaustion, and high expression of inhibitory molecules. Cells with a Teee gene signature were present in tumors of patients with melanoma, lung, and bladder cancers. CD4+ T cells co-expressing CD38 and CD39 in the tumor microenvironment were preferentially associated with Ki67− CD8+ T cells. Co-culture of patient Teee with autologous T cells resulted in decreased proliferation of target T cells. High baseline intratumoral frequencies of Teee were associated with checkpoint immunotherapy resistance and poor overall survival in patients with metastatic melanoma.
Conclusions:
These results demonstrate that a novel population of CD4+ T cells co-expressing CD38 and CD39 is found both in the peripheral blood and tumor of patients with melanoma and is associated with checkpoint immunotherapy resistance.
Data from Memory-like Differentiation, Tumor-Targeting mAbs, and Chimeric Antigen Receptors Enhance Natural Killer Cell Responses to Head and Neck Cancer
Authors: Jacobs Miriam T. , Wong Pamela , Zhou Alice Y. , Becker-Hapak Michelle , Marin Nancy D. , Marsala Lynne , Foster Mark , Foltz Jennifer A. , Cubitt Celia C. , Tran Jennifer , Russler-Germain David A. , Neal Carly , Kersting-Schadek Samantha , Chang Lily , Schappe Timothy , Pence Patrick , McClain Ethan , Zevallos Jose P. , Rich Jason T. , Paniello Randal C. , Jackson Ryan S. , Pipkorn Patrik , Adkins Douglas R. , DeSelm Carl J. , Berrien-Elliott Melissa M. , Puram Sidharth V. , Fehniger Todd A.
Published: October 2023

AbstractPurpose:
Head and neck squamous cell carcinoma (HNSCC) is an aggressive tumor with low response rates to frontline PD-1 blockade. Natural killer (NK) cells are a promising cellular therapy for T cell therapy–refractory cancers, but are frequently dysfunctional in patients with HNSCC. Strategies are needed to enhance NK cell responses against HNSCC. We hypothesized that memory-like (ML) NK cell differentiation, tumor targeting with cetuximab, and engineering with an anti-EphA2 (Erythropoietin-producing hepatocellular receptor A2) chimeric antigen receptor (CAR) enhance NK cell responses against HNSCC.
Experimental Design:
We generated ML NK and conventional (c)NK cells from healthy donors, then evaluated their ability to produce IFNγ, TNF, degranulate, and kill HNSCC cell lines and primary HNSCC cells, alone or in combination with cetuximab, in vitro and in vivo using xenograft models. ML and cNK cells were engineered to express anti-EphA2 CAR-CD8A-41BB-CD3z, and functional responses were assessed in vitro against HNSCC cell lines and primary HNSCC tumor cells.
Results:
Human ML NK cells displayed enhanced IFNγ and TNF production and both short- and long-term killing of HNSCC cell lines and primary targets, compared with cNK cells. These enhanced responses were further improved by cetuximab. Compared with controls, ML NK cells expressing anti-EphA2 CAR had increased IFNγ and cytotoxicity in response to EphA2+ cell lines and primary HNSCC targets.
Conclusions:
These preclinical findings demonstrate that ML differentiation alone or coupled with either cetuximab-directed targeting or EphA2 CAR engineering were effective against HNSCCs and provide the rationale for investigating these combination approaches in early phase clinical trials for patients with HNSCC.
Data from Baseline mutations and ctDNA dynamics as prognostic and predictive factors in ER-positive/HER2-negative metastatic breast cancer patients
Authors: Pascual Javier , Gil-Gil Miguel , Proszek Paula , Zielinski Christoph , Reay Alistair , Ruiz-Borrego Manuel , Cutts Rosalind , Ciruelos Gil Eva M. , Feber Andrew , Muñoz-Mateu Montserrat , Swift Claire , Bermejo Begoña , Herranz Jesus , Margeli Vila Mireia , Antón Antonio , Kahan Zsuzsanna , Csöszi Tibor , Liu Yuan , Fernandez Garcia Daniel , Garcia-Murillas Isaac , Hubank Michael , Turner Nicholas C. , Martín Miguel
Published: October 2023

Abstract
Purpose: Prognostic and predictive biomarkers to CDK4/6 inhibitors are lacking. Circulating tumour DNA (ctDNA) can be used to profile these patients and dynamic changes in ctDNA could be an early predictor of treatment efficacy. Here, we conducted plasma ctDNA profiling in patients from the PEARL trial comparing palbociclib+fulvestrant versus capecitabine to investigate associations between baseline genomic landscape and on-treatment ctDNA dynamics with treatment efficacy. Experimental Design: Correlative blood samples were collected at baseline (C1D1) and prior to treatment (C1D15). Plasma ctDNA was sequenced with a custom error-corrected capture panel, with both univariate and multivariate Cox models used for treatment efficacy associations. A pre-specified methodology measuring ctDNA changes in clonal mutations between C1D1 and C1D15 was used for the on-treatment ctDNA dynamic model. Results: 201 patients were profiled at baseline, with ctDNA detection associated with worse PFS/OS. Detectable TP53 mutation showed worse PFS and OS in both treatment arms, even after restricting population to baseline ctDNA detection. ESR1 mutations were associated with worse OS overall, which was lost when restricting population to baseline ctDNA detection. PIK3CA mutations confer worse OS only to patients on the palbociclib+fulvestrant treatment arm. ctDNA dynamics analysis (n=120) showed higher ctDNA suppression in the capecitabine arm. Patients without ctDNA suppression showed worse PFS in both treatment arms. Conclusions: We show impaired survival irrespective of endocrine or chemotherapy-based treatments for patients with HR+/HER2- MBC harbouring plasma TP53 mutations. Early ctDNA suppression may provide treatment efficacy predictions. Further validation to fully demonstrate clinical utility of ctDNA dynamics is warranted.
Data from Specific Targeting of Multiple Myeloma by Dual Split-signaling Chimeric Antigen Receptor T cells Directed against CD38 and CD138
Authors: van der Schans Jort J. , Wang Ziyu , van Arkel Jennemiek , van Schaik Thijs , Katsarou Afroditi , Ruiter Ruud , Baardemans Thomas , Yuan Huipin , de Bruijn Joost , Zweegman Sonja , van de Donk Niels W.C.J. , Groen Richard W.J. , Themeli Maria , Mutis Tuna
Published: October 2023

AbstractPurpose:
The success of B-cell maturation antigen (BCMA)-specific chimeric antigen receptor (CAR) T cells illustrates the potential of this novel therapy for multiple myeloma. Nonetheless, broadening CAR T-cell therapy beyond BCMA requires inventive strategies as there are only a few multiple myeloma– or plasma cell–specific target antigens. We investigated the feasibility of achieving multiple myeloma specificity by dual-split CD38/CD138 CAR targeting, whereby the stimulatory and costimulatory signals for T-cell activation are split into two separate stimulatory (sCAR) and costimulatory CARs (cCAR).
Experimental Design:
Using various combinations of CD38 and CD138 sCARs and cCARs with different affinities, we generated several dual-split CAR T cells and analyzed them for multiple myeloma–specific effector functions in vitro. The best-functioning CAR T cells were tested in vivo in a murine xenograft model.
Results:
We found optimal designs of both CD38sCAR/CD138cCAR and CD138sCAR/CD38cCAR combinations, that effectively lysed multiple myeloma cells but spared single CD38- or CD138-positive healthy hematopoietic cells. While the CD38sCAR/CD138cCAR T cells achieved multiple myeloma–specific activity solely due to the low affinity of the CD38sCARs, the multiple myeloma–specific cytotoxicity, cytokine release, and proliferation of CD138sCAR/CD38cCAR T cells were established through a true combinatorial stimulatory and costimulatory effect. The most optimal combination comprised a low-affinity CD138sCAR combined with a high-affinity CD38cCAR. These CD138sCAR/CD38cCAR T cells also showed dual-antigen specific anti–multiple myeloma effects in vivo. Importantly, they were also effective against multiple myeloma cells from daratumumab pretreated patients with decreased CD38 expression levels.
Conclusions:
We demonstrate the possibility to specifically target multiple myeloma cells, even after CD38 targeted therapy, with carefully-designed dual-split CARs directed against CD38 and CD138.