bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplementary Figure S6 from (R)-2-Hydroxyglutarate Inhibits KDM5 Histone Lysine Demethylases to Drive Transformation in IDH-Mutant Cancers
Authors: Gunn Kathryn , Myllykoski Matti , Cao John Z. , Ahmed Manna , Huang Bofu , Rouaisnel Betty , Diplas Bill H. , Levitt Michael M. , Looper Ryan , Doench John G. , Ligon Keith L. , Kornblum Harley I. , McBrayer Samuel K. , Yan Hai , Duy Cihangir , Godley Lucy A. , Koivunen Peppi , Losman Julie-Aurore
Published: June 2023

Transcriptional analysis of primary AML patient samples.
Supplementary Figure S4 from (R)-2-Hydroxyglutarate Inhibits KDM5 Histone Lysine Demethylases to Drive Transformation in IDH-Mutant Cancers
Authors: Gunn Kathryn , Myllykoski Matti , Cao John Z. , Ahmed Manna , Huang Bofu , Rouaisnel Betty , Diplas Bill H. , Levitt Michael M. , Looper Ryan , Doench John G. , Ligon Keith L. , Kornblum Harley I. , McBrayer Samuel K. , Yan Hai , Duy Cihangir , Godley Lucy A. , Koivunen Peppi , Losman Julie-Aurore
Published: June 2023

ChIP-seq analysis of primary AML patient samples.
Supplementary Figure S3 from (R)-2-Hydroxyglutarate Inhibits KDM5 Histone Lysine Demethylases to Drive Transformation in IDH-Mutant Cancers
Authors: Gunn Kathryn , Myllykoski Matti , Cao John Z. , Ahmed Manna , Huang Bofu , Rouaisnel Betty , Diplas Bill H. , Levitt Michael M. , Looper Ryan , Doench John G. , Ligon Keith L. , Kornblum Harley I. , McBrayer Samuel K. , Yan Hai , Duy Cihangir , Godley Lucy A. , Koivunen Peppi , Losman Julie-Aurore
Published: June 2023

Trimethyl-H3K4 is not enriched upon knock-down of TET2 in TF-1 cells.
Supplementary Figure S2 from (R)-2-Hydroxyglutarate Inhibits KDM5 Histone Lysine Demethylases to Drive Transformation in IDH-Mutant Cancers
Authors: Gunn Kathryn , Myllykoski Matti , Cao John Z. , Ahmed Manna , Huang Bofu , Rouaisnel Betty , Diplas Bill H. , Levitt Michael M. , Looper Ryan , Doench John G. , Ligon Keith L. , Kornblum Harley I. , McBrayer Samuel K. , Yan Hai , Duy Cihangir , Godley Lucy A. , Koivunen Peppi , Losman Julie-Aurore
Published: June 2023

Inhibition of KDM5 enzymes by the (R)- and (S)-enantiomers of 2-hydroxyglutarate.
Supplementary Figure S10 from (R)-2-Hydroxyglutarate Inhibits KDM5 Histone Lysine Demethylases to Drive Transformation in IDH-Mutant Cancers
Authors: Gunn Kathryn , Myllykoski Matti , Cao John Z. , Ahmed Manna , Huang Bofu , Rouaisnel Betty , Diplas Bill H. , Levitt Michael M. , Looper Ryan , Doench John G. , Ligon Keith L. , Kornblum Harley I. , McBrayer Samuel K. , Yan Hai , Duy Cihangir , Godley Lucy A. , Koivunen Peppi , Losman Julie-Aurore
Published: June 2023

Prolonged exposure to MLL inhibitor VTP50469 does not affect the proliferation of TF-1 cells grown under cytokine-rich conditions.
Supplementary Tables 1-7 from Combinatorial BCL2 Family Expression in Acute Myeloid Leukemia Stem Cells Predicts Clinical Response to Azacitidine/Venetoclax
Authors: Waclawiczek Alexander , Leppä Aino-Maija , Renders Simon , Stumpf Karolin , Reyneri Cecilia , Betz Barbara , Janssen Maike , Shahswar Rabia , Donato Elisa , Karpova Darja , Thiel Vera , Unglaub Julia M. , Grabowski Susanna , Gryzik Stefanie , Vierbaum Lisa , Schlenk Richard F. , Röllig Christoph , Hundemer Michael , Pabst Caroline , Heuser Michael , Raffel Simon , Müller-Tidow Carsten , Sauer Tim , Trumpp Andreas
Published: June 2023

7 Tables showing: molecular and clinical patient data, cell line info, antibody panels and overview of assays used
Supplementary Figure 4 from Combinatorial BCL2 Family Expression in Acute Myeloid Leukemia Stem Cells Predicts Clinical Response to Azacitidine/Venetoclax
Authors: Waclawiczek Alexander , Leppä Aino-Maija , Renders Simon , Stumpf Karolin , Reyneri Cecilia , Betz Barbara , Janssen Maike , Shahswar Rabia , Donato Elisa , Karpova Darja , Thiel Vera , Unglaub Julia M. , Grabowski Susanna , Gryzik Stefanie , Vierbaum Lisa , Schlenk Richard F. , Röllig Christoph , Hundemer Michael , Pabst Caroline , Heuser Michael , Raffel Simon , Müller-Tidow Carsten , Sauer Tim , Trumpp Andreas
Published: June 2023

Subpopulation specific Bcl-2 family levels and response to HMA/Venetoclax
Data from A transcriptome-based precision oncology platform for patient-therapy alignment in a diverse set of treatment resistant malignancies
Authors: Mundi Prabhjot S. , Dela Cruz Filemon S. , Grunn Adina , Diolaiti Daniel , Mauguen Audrey , Rainey Allison R. , Guillan Kristina , Siddiquee Armaan , You Daoqi , Realubit Ronald , Karan Charles , Ortiz Michael V. , Douglass Eugene F. , Accordino Melissa , Mistretta Suzanne , Brogan Frances , Bruce Jeffrey N. , Caescu Cristina I. , Carvajal Richard D. , Crew Katherine D. , Decastro Guarionex , Heaney Mark , Henick Brian S. , Hershman Dawn L. , Hou June Y. , Iwamoto Fabio M. , Jurcic Joseph G. , Kiran Ravi P. , Kluger Michael D. , Kreisl Teri , Lamanna Nicole , Lassman Andrew B. , Lim Emerson A. , Manji Gulam A. , McKhann Guy M. , McKiernan James M. , Neugut Alfred I. , Olive Kenneth P. , Rosenblat Todd , Schwartz Gary K. , Shu Catherine A. , Sisti Michael B. , Tergas Ana , Vattakalam Reena M. , Welch Mary , Wenske Sven , Wright Jason D. , Canoll Peter , Hibshoosh Hanina , Kalinsky Kevin , Aburi Mahalaxmi , Sims Peter A. , Alvarez Mariano J. , Kung Andrew L. , Califano Andrea
Published: June 2023

Abstract
Predicting in vivo response to antineoplastics remains an elusive challenge. We performed first-of-kind evaluation of two transcriptome-based precision cancer medicine methodologies to predict tumor sensitivity to a comprehensive repertoire of clinically relevant oncology drugs, whose mechanism-of-action we experimentally assessed in cognate cell lines. We enrolled patients with histologically distinct, poor prognosis malignancies who had progressed on multiple therapies, and developed low-passage, patient-derived xenograft models that were used to validate 35 patient-specific drug predictions. Both OncoTarget, which identifies high-affinity inhibitors of individual Master Regulator (MR) proteins, and OncoTreat, which identifies drugs that invert the transcriptional activity of hyper-connected MR modules, produced highly significant 30-day disease control rates (68% and 91%, respectively). Moreover, of 18 OncoTreat-predicted drugs, 15 induced the predicted MR-module activity inversion in vivo. Predicted drugs significantly outperformed antineoplastic drugs selected as unpredicted controls, suggesting these methods may substantively complement existing PCM approaches, as also illustrated by a case study.
Bridging the Gap between Diseases of the Stomach and Lower Esophagus
Authors: Stachler Matthew D.
Published: June 2023

In this issue of Cancer Discovery, Nowicki-Osuch and colleagues perform an extensive characterization and analysis of single-cell RNA-sequencing data of the tubal gastrointestinal system, including a spectrum of inflammatory conditions and intestinal metaplasia of the stomach and esophagus. They show that both gastric and esophageal intestinal metaplasia share similarities at the transcript and protein levels. Interestingly, they show that individual cells within areas of metaplasia can coexpress transcriptional programs of both gastric and intestinal epithelia.

See related article by Nowicki-Osuch et al., 1346 (6).
Supplementary Tables from Influence of Adipose Tissue Distribution, Sarcopenia, and Nutritional Status on Clinical Outcomes After CD19 CAR T-cell Therapy
Authors: Rejeski Kai , Cordas dos Santos David M. , Parker Nathan H. , Bücklein Veit L. , Winkelmann Michael , Jhaveri Khushali S. , Liu Lian , Trinkner Paul , Günther Sophie , Karschnia Philipp , Blumenberg Viktoria , Schmidt Christian , Kunz Wolfgang G. , von Bergwelt-Baildon Michael , Jain Michael D. , Theurich Sebastian , Subklewe Marion
Published: June 2023

Supplementary Tables
Supplementary Figures from Influence of Adipose Tissue Distribution, Sarcopenia, and Nutritional Status on Clinical Outcomes After CD19 CAR T-cell Therapy
Authors: Rejeski Kai , Cordas dos Santos David M. , Parker Nathan H. , Bücklein Veit L. , Winkelmann Michael , Jhaveri Khushali S. , Liu Lian , Trinkner Paul , Günther Sophie , Karschnia Philipp , Blumenberg Viktoria , Schmidt Christian , Kunz Wolfgang G. , von Bergwelt-Baildon Michael , Jain Michael D. , Theurich Sebastian , Subklewe Marion
Published: June 2023

Supplementary Figures
Supplementary Data from EBV-Upregulated B7-H3 Inhibits NK cell–Mediated Antitumor Function and Contributes to Nasopharyngeal Carcinoma Progression
Authors: Chen Haiwen , Duan Xiaobing , Deng Xiaohong , Huang Yingping , Zhou Xiang , Zhang Shanshan , Zhang Xiao , Liu Pingjuan , Yang Chaopin , Liu Guojun , Ren Qinqin , Xiong Yan , Zhu Bo , Zhang Jiexia , Xiang Tong
Published: June 2023

Supplementary Figures and Tables
Supplementary Table 2 from Regional Variation in the Tumor Microenvironment, Immune Escape and Prognostic Factors in Breast Cancer in Sub-Saharan Africa
Authors: Bauer Marcus , Vetter Martina , Stückrath Kathrin , Yohannes Meron , Desalegn Zelalem , Yalew Tewodros , Bekuretsion Yonas , Kenea Tariku W. , Joffe Maureen , van den Berg Eunice J. , Nikulu Julien 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: June 2023

Supplementary Table 2
Supplementary Table 1 from Regional Variation in the Tumor Microenvironment, Immune Escape and Prognostic Factors in Breast Cancer in Sub-Saharan Africa
Authors: Bauer Marcus , Vetter Martina , Stückrath Kathrin , Yohannes Meron , Desalegn Zelalem , Yalew Tewodros , Bekuretsion Yonas , Kenea Tariku W. , Joffe Maureen , van den Berg Eunice J. , Nikulu Julien 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: June 2023

Supplementary Table 1
Supplementary Figure 6 from Regional Variation in the Tumor Microenvironment, Immune Escape and Prognostic Factors in Breast Cancer in Sub-Saharan Africa
Authors: Bauer Marcus , Vetter Martina , Stückrath Kathrin , Yohannes Meron , Desalegn Zelalem , Yalew Tewodros , Bekuretsion Yonas , Kenea Tariku W. , Joffe Maureen , van den Berg Eunice J. , Nikulu Julien 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: June 2023

Figure S6: Multivariate Cox regression analysis of patient's survival.
Supplementary Figure 5 from Regional Variation in the Tumor Microenvironment, Immune Escape and Prognostic Factors in Breast Cancer in Sub-Saharan Africa
Authors: Bauer Marcus , Vetter Martina , Stückrath Kathrin , Yohannes Meron , Desalegn Zelalem , Yalew Tewodros , Bekuretsion Yonas , Kenea Tariku W. , Joffe Maureen , van den Berg Eunice J. , Nikulu Julien 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: June 2023

Figure S5: MHC I expression in SSA
Supplementary Figure 3 from Regional Variation in the Tumor Microenvironment, Immune Escape and Prognostic Factors in Breast Cancer in Sub-Saharan Africa
Authors: Bauer Marcus , Vetter Martina , Stückrath Kathrin , Yohannes Meron , Desalegn Zelalem , Yalew Tewodros , Bekuretsion Yonas , Kenea Tariku W. , Joffe Maureen , van den Berg Eunice J. , Nikulu Julien 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: June 2023

Figure S3: Immune cell subpopulations in SSA
Supplementary Figure 2 from Regional Variation in the Tumor Microenvironment, Immune Escape and Prognostic Factors in Breast Cancer in Sub-Saharan Africa
Authors: Bauer Marcus , Vetter Martina , Stückrath Kathrin , Yohannes Meron , Desalegn Zelalem , Yalew Tewodros , Bekuretsion Yonas , Kenea Tariku W. , Joffe Maureen , van den Berg Eunice J. , Nikulu Julien 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: June 2023

Figure S2: TILs in SSA
Supplementary Figure 1 from Regional Variation in the Tumor Microenvironment, Immune Escape and Prognostic Factors in Breast Cancer in Sub-Saharan Africa
Authors: Bauer Marcus , Vetter Martina , Stückrath Kathrin , Yohannes Meron , Desalegn Zelalem , Yalew Tewodros , Bekuretsion Yonas , Kenea Tariku W. , Joffe Maureen , van den Berg Eunice J. , Nikulu Julien 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: June 2023

Figure S1: Consort diagram of the analyzed samples
Table 1 from The Immunopeptidome from a Genomic Perspective: Establishing the Noncanonical Landscape of MHC Class I–Associated Peptides
Authors: Bedran Georges , Gasser Hans-Christof , Weke Kenneth , Wang Tongjie , Bedran Dominika , Laird Alexander , Battail Christophe , Zanzotto Fabio Massimo , Pesquita Catia , Axelson Håkan , Rajan Ajitha , Harrison David J. , Palkowski Aleksander , Pawlik Maciej , Parys Maciej , O'Neill J. Robert , Brennan Paul M. , Symeonides Stefan N. , Goodlett David R. , Litchfield Kevin , Fahraeus Robin , Hupp Ted R. , Kote Sachin , Alfaro Javier A.
Published: June 2023

List of cancer-selective noncanonical MHC-associated peptides.
Supplementary Tables from iBRIDGE: A Data Integration Method to Identify Inflamed Tumors from Single-cell RNA-Seq Data and Differentiate Cell Type–Specific Markers of Immune-Cell Infiltration
Authors: Turan Tolga , Kongpachith Sarah , Halliwill Kyle , McLaughlin Robert T. , Binnewies Mikhail , Reddy Dhemath , Zhao Xi , Mathew Rebecca , Ye Shiming , Jacob Howard J. , Samayoa Josue
Published: June 2023

Supplementary Tables S1-S16
Supplementary notes from The Immunopeptidome from a Genomic Perspective: Establishing the Noncanonical Landscape of MHC Class I–Associated Peptides
Authors: Bedran Georges , Gasser Hans-Christof , Weke Kenneth , Wang Tongjie , Bedran Dominika , Laird Alexander , Battail Christophe , Zanzotto Fabio Massimo , Pesquita Catia , Axelson Håkan , Rajan Ajitha , Harrison David J. , Palkowski Aleksander , Pawlik Maciej , Parys Maciej , O'Neill J. Robert , Brennan Paul M. , Symeonides Stefan N. , Goodlett David R. , Litchfield Kevin , Fahraeus Robin , Hupp Ted R. , Kote Sachin , Alfaro Javier A.
Published: June 2023

Supplementary notes 1 and 2.
Supplementary Figures from iBRIDGE: A Data Integration Method to Identify Inflamed Tumors from Single-cell RNA-Seq Data and Differentiate Cell Type–Specific Markers of Immune-Cell Infiltration
Authors: Turan Tolga , Kongpachith Sarah , Halliwill Kyle , McLaughlin Robert T. , Binnewies Mikhail , Reddy Dhemath , Zhao Xi , Mathew Rebecca , Ye Shiming , Jacob Howard J. , Samayoa Josue
Published: June 2023

Supplementary Figures S1-S6
Supplementary figures from The Immunopeptidome from a Genomic Perspective: Establishing the Noncanonical Landscape of MHC Class I–Associated Peptides
Authors: Bedran Georges , Gasser Hans-Christof , Weke Kenneth , Wang Tongjie , Bedran Dominika , Laird Alexander , Battail Christophe , Zanzotto Fabio Massimo , Pesquita Catia , Axelson Håkan , Rajan Ajitha , Harrison David J. , Palkowski Aleksander , Pawlik Maciej , Parys Maciej , O'Neill J. Robert , Brennan Paul M. , Symeonides Stefan N. , Goodlett David R. , Litchfield Kevin , Fahraeus Robin , Hupp Ted R. , Kote Sachin , Alfaro Javier A.
Published: June 2023

Supplementary Figures S1 to S7.
Supplementary Table 5 from The Immunopeptidome from a Genomic Perspective: Establishing the Noncanonical Landscape of MHC Class I–Associated Peptides
Authors: Bedran Georges , Gasser Hans-Christof , Weke Kenneth , Wang Tongjie , Bedran Dominika , Laird Alexander , Battail Christophe , Zanzotto Fabio Massimo , Pesquita Catia , Axelson Håkan , Rajan Ajitha , Harrison David J. , Palkowski Aleksander , Pawlik Maciej , Parys Maciej , O'Neill J. Robert , Brennan Paul M. , Symeonides Stefan N. , Goodlett David R. , Litchfield Kevin , Fahraeus Robin , Hupp Ted R. , Kote Sachin , Alfaro Javier A.
Published: June 2023

Mapping of ncMAPs to COSMIC frameshift mutations.
Supplementary Video S2 MMP14 from Breast Cancer Stem Cell–Derived Tumors Escape from γδ T-cell Immunosurveillance In Vivo by Modulating γδ T-cell Ligands
Authors: Raute Katrin , Strietz Juliane , Parigiani Maria Alejandra , Andrieux Geoffroy , Thomas Oliver S. , Kistner Klaus M. , Zintchenko Marina , Aichele Peter , Hofmann Maike , Zhou Houjiang , Weber Wilfried , Boerries Melanie , Swamy Mahima , Maurer Jochen , Minguet Susana
Published: June 2023

Supplementary Video S2 MMP14
Supplementary Table 3 from The Immunopeptidome from a Genomic Perspective: Establishing the Noncanonical Landscape of MHC Class I–Associated Peptides
Authors: Bedran Georges , Gasser Hans-Christof , Weke Kenneth , Wang Tongjie , Bedran Dominika , Laird Alexander , Battail Christophe , Zanzotto Fabio Massimo , Pesquita Catia , Axelson Håkan , Rajan Ajitha , Harrison David J. , Palkowski Aleksander , Pawlik Maciej , Parys Maciej , O'Neill J. Robert , Brennan Paul M. , Symeonides Stefan N. , Goodlett David R. , Litchfield Kevin , Fahraeus Robin , Hupp Ted R. , Kote Sachin , Alfaro Javier A.
Published: June 2023

Annotation of the COD-dipp ncMAPs.
Supplementary Video S1 UT from Breast Cancer Stem Cell–Derived Tumors Escape from γδ T-cell Immunosurveillance In Vivo by Modulating γδ T-cell Ligands
Authors: Raute Katrin , Strietz Juliane , Parigiani Maria Alejandra , Andrieux Geoffroy , Thomas Oliver S. , Kistner Klaus M. , Zintchenko Marina , Aichele Peter , Hofmann Maike , Zhou Houjiang , Weber Wilfried , Boerries Melanie , Swamy Mahima , Maurer Jochen , Minguet Susana
Published: June 2023

Supplementary Video S1 UT
Supplementary Table 2 from The Immunopeptidome from a Genomic Perspective: Establishing the Noncanonical Landscape of MHC Class I–Associated Peptides
Authors: Bedran Georges , Gasser Hans-Christof , Weke Kenneth , Wang Tongjie , Bedran Dominika , Laird Alexander , Battail Christophe , Zanzotto Fabio Massimo , Pesquita Catia , Axelson Håkan , Rajan Ajitha , Harrison David J. , Palkowski Aleksander , Pawlik Maciej , Parys Maciej , O'Neill J. Robert , Brennan Paul M. , Symeonides Stefan N. , Goodlett David R. , Litchfield Kevin , Fahraeus Robin , Hupp Ted R. , Kote Sachin , Alfaro Javier A.
Published: June 2023

Open search peptide-spectrum matches (PSMs) information of serine acetylation, cysteinylation, carbamidomethylation, and cysteine trioxidation.
Supplementary Figures and Figure Legends from Breast Cancer Stem Cell–Derived Tumors Escape from γδ T-cell Immunosurveillance In Vivo by Modulating γδ T-cell Ligands
Authors: Raute Katrin , Strietz Juliane , Parigiani Maria Alejandra , Andrieux Geoffroy , Thomas Oliver S. , Kistner Klaus M. , Zintchenko Marina , Aichele Peter , Hofmann Maike , Zhou Houjiang , Weber Wilfried , Boerries Melanie , Swamy Mahima , Maurer Jochen , Minguet Susana
Published: June 2023

Supplementary Figures and Figure Legends
Figure 6 from The Immunopeptidome from a Genomic Perspective: Establishing the Noncanonical Landscape of MHC Class I–Associated Peptides
Authors: Bedran Georges , Gasser Hans-Christof , Weke Kenneth , Wang Tongjie , Bedran Dominika , Laird Alexander , Battail Christophe , Zanzotto Fabio Massimo , Pesquita Catia , Axelson Håkan , Rajan Ajitha , Harrison David J. , Palkowski Aleksander , Pawlik Maciej , Parys Maciej , O'Neill J. Robert , Brennan Paul M. , Symeonides Stefan N. , Goodlett David R. , Litchfield Kevin , Fahraeus Robin , Hupp Ted R. , Kote Sachin , Alfaro Javier A.
Published: June 2023

Cancer selectivity of ncMAPs. A, Percentage of ncMAPs that were solely in healthy and/or tumor samples by MS (blue) and ncMAPs undetected in healthy samples by MS (red). B, Parent gene expression of ncMAPs in TPM in 29 healthy tissues from 17,382 samples (GTEx v8 dataset). ncMAPs are distributed over two groups: ncMAPs detected in healthy samples by MS in blue, and ncMAPs undetected in healthy samples by MS in red. C, Parent gene expression of ncMAPs in TPM in 29 healthy tissues from 17,382 samples (GTEx v8 dataset). A limit on the gene expression (y-axis) of 1.2 TPM was set to visualize cancer-selective ncMAPs in black.
Figure 6 from Breast Cancer Stem Cell–Derived Tumors Escape from γδ T-cell Immunosurveillance In Vivo by Modulating γδ T-cell Ligands
Authors: Raute Katrin , Strietz Juliane , Parigiani Maria Alejandra , Andrieux Geoffroy , Thomas Oliver S. , Kistner Klaus M. , Zintchenko Marina , Aichele Peter , Hofmann Maike , Zhou Houjiang , Weber Wilfried , Boerries Melanie , Swamy Mahima , Maurer Jochen , Minguet Susana
Published: June 2023

BCSCs differentiate in vivo and downregulate the expression of proteins recognized by γδ T cells. A, Rowwise Z-score heat maps showing upregulated and downregulated proteins in BCSC5 culture cells or xenograft-derived tumors from two or three biological replicates as indicated (BR). B, Rowwise Z-score heat map for proteins involved in target cell recognition by γδ T cells or in immune response modulation. C, Flow cytometry-based analysis of BCSC5 culture cells and xenograft-derived tumor cells. MFI of at least five tumors per group is shown (median, minimum to maximum). One-way ANOVA followed by Dunnett post hoc test comparing xenograft-derived cells with culture cells (for ULBP2/5/6, ICAM-1, and BTN3A). Kruskal-Wallis test followed by Dunn post hoc test comparing xenograft-derived cells with culture cells (for Fas, TRAILR1, and TRAILR2). D, Killing of BCSC5 by γδ T cells requires multiple ligand–receptors interactions. In vitro killing of luciferase-expressing BCSC5 cells by γδ T cells. γδ T cells or BCSC5 culture cells were pretreated with the indicated blocking antibodies for 1 hour. Cells were cocultured at an E:T ratio of 10:1 for 8 hours in the presence of the blocking antibodies or the corresponding isotype controls. Corresponding receptor-ligand pairs are represented in the same color. Isotype antibody control was set to 100% for normalization in each experiment. Results for 3 to 4 healthy donors of γδ T cells from three independent experiments were pooled (means ± SEM). One-sample t test against hypothetical value of 100. E, Cox regression of progression-free survival for patients with TNBC sorted by high (top quartile) and low (bottom quartile) average clustered expression of the Fas, MICB, and ICAM-1. β Cox coefficient was −0.33 and the Cox P value was 0.07 suggesting that high expression of the three proteins correlates with a better survival prognosis. *, P ≤ 0.05; **, P ≤ 0.01; ***, P ≤ 0.001; ****, P ≤ 0.0001.
Figure 5 from The Immunopeptidome from a Genomic Perspective: Establishing the Noncanonical Landscape of MHC Class I–Associated Peptides
Authors: Bedran Georges , Gasser Hans-Christof , Weke Kenneth , Wang Tongjie , Bedran Dominika , Laird Alexander , Battail Christophe , Zanzotto Fabio Massimo , Pesquita Catia , Axelson Håkan , Rajan Ajitha , Harrison David J. , Palkowski Aleksander , Pawlik Maciej , Parys Maciej , O'Neill J. Robert , Brennan Paul M. , Symeonides Stefan N. , Goodlett David R. , Litchfield Kevin , Fahraeus Robin , Hupp Ted R. , Kote Sachin , Alfaro Javier A.
Published: June 2023

Origins of ncMAPs. A, Peptide length distribution of canonical (dark gray) and noncanonical (light gray) MAPs. B, Annotation of ncMAPs across gene features. C, Analysis of ncMAPs that could originate from nORF. Upstream start codons of noncanonical MAPs are analyzed for their potential to initiate translation and produce ORFs (left-hand side) as a source of ncMAPs. The frequencies of different start codons for positively predicted TIS are shown on the right-hand side. D, Analysis of ncMAPs from intronic regions that may originate from IR events. Translation of MAPs from IR sources should be in-frame with the corresponding upstream exons. E, Analysis of ncMAPs that could originate from frameshift mutations in cancer. ncMAPs are aligned to an in-silico translated protein database of COSMIC somatic frameshift mutations. F, Summary indicating whether the ncMAPs can be accounted for by any of the analyses conducted in panels C, D, or E.
Figure 5 from Breast Cancer Stem Cell–Derived Tumors Escape from γδ T-cell Immunosurveillance In Vivo by Modulating γδ T-cell Ligands
Authors: Raute Katrin , Strietz Juliane , Parigiani Maria Alejandra , Andrieux Geoffroy , Thomas Oliver S. , Kistner Klaus M. , Zintchenko Marina , Aichele Peter , Hofmann Maike , Zhou Houjiang , Weber Wilfried , Boerries Melanie , Swamy Mahima , Maurer Jochen , Minguet Susana
Published: June 2023

BCSCs phenotypically change in vivo, but still induce γδ T-cell migration. A, The proteomes of BCSC5 culture cells or freshly isolated xenograft-derived tumor cells were analyzed by mass spectrometry. Volcano plot showing differentially expressed proteins. Proteins regulated with P < 0.05 are depicted in red. B, Rowwise Z-score heat maps showing upregulated and downregulated proteins in BCSC5 culture cells or xenograft-derived tumors from two or three biological replicates (BR) as indicated. C, Migration of γδ T cells (CD3+γδTCR+) in response to BCSC5 culture cells and xenograft-derived tumor cells was determined in a transwell assay. Basal migration towards medium was set to 1.0 and fold changes from three independent experiments using the same 3 healthy donors in each experiment were pooled and analyzed using one-sample Wilcoxon test. D, Migration of Vδ1+ (CD3+γδTCR+Vδ1+) and Vδ2+(CD3+γδTCR+Vδ2+) T cells in response to BCSC5 culture cells and xenograft-derived tumor cells was determined in a transwell assay. Basal migration toward medium was set to 1.0 and fold changes from three independent experiments using the same 3 healthy donors in each experiment were pooled. One-sample t test (for Vδ1+) or one-sample Wilcoxon test (for Vδ2+). *, P ≤ 0.05; **, P ≤ 0.01; ****, P ≤ 0.0001. Non-adj., non-adjusted.
Figure 4 from The Immunopeptidome from a Genomic Perspective: Establishing the Noncanonical Landscape of MHC Class I–Associated Peptides
Authors: Bedran Georges , Gasser Hans-Christof , Weke Kenneth , Wang Tongjie , Bedran Dominika , Laird Alexander , Battail Christophe , Zanzotto Fabio Massimo , Pesquita Catia , Axelson Håkan , Rajan Ajitha , Harrison David J. , Palkowski Aleksander , Pawlik Maciej , Parys Maciej , O'Neill J. Robert , Brennan Paul M. , Symeonides Stefan N. , Goodlett David R. , Litchfield Kevin , Fahraeus Robin , Hupp Ted R. , Kote Sachin , Alfaro Javier A.
Published: June 2023

Comparison of COD-dipp ncMAPs with other studies. Because the COD-dipp ncMAPs are restricted to the 3-frame translation (3FT) of protein-coding genes, sequences from the literature were aligned to the same 3FT database for comparison purposes. The intersection is based on genomic coordinates to deal with sequences that partially match (i.e., longer, shorter, or partially overlapping). Because the Venn is generated by overlapping genomic coordinates of the ncMAPs, the original counts for each study are listed from left to right (i.e., on the right-hand side of panel C, the notation 29/41 refers to 29 instances for Chong and colleagues 2020 and 41 for COD-dipp). A, Comparison with peptide-PRISM published ncMAPs at a 10% FDR. COD-dipp ncMAPs were restricted to 3 studies in common with Erhard and colleagues 2020. B, Comparison with peptide-PRISM published ncMAPs at a 1% FDR. COD-dipp ncMAPs were restricted to 3 studies in common with Erhard and colleagues 2020. C, Comparison of the atlas of ncMAPs revealed by COD-dipp to 3 previous studies.
Figure 3 from Breast Cancer Stem Cell–Derived Tumors Escape from γδ T-cell Immunosurveillance In Vivo by Modulating γδ T-cell Ligands
Authors: Raute Katrin , Strietz Juliane , Parigiani Maria Alejandra , Andrieux Geoffroy , Thomas Oliver S. , Kistner Klaus M. , Zintchenko Marina , Aichele Peter , Hofmann Maike , Zhou Houjiang , Weber Wilfried , Boerries Melanie , Swamy Mahima , Maurer Jochen , Minguet Susana
Published: June 2023

MMP14 expression increases γδ T-cell migration in basement membrane-like Matrigel and in BCSC5 tumor tissue. A, Representative dot plots (left) and histograms (right) of γδ T cells expressing mock, MMP14, or MMP14E240A on day 3 after transduction with a MOI of 5. UT cells served as control. B, Schematic illustration of the 3D migration assay in Matrigel (left). γδ T cells were seeded into ibidi μ-angiogenesis slides in 100% Matrigel. Migration toward medium supplemented with 10% FBS and 50 ng/mL CXCL12 was assessed via confocal microscopy after 48 hours. Statistical analysis (right) of the percent of γδ T cells migrating further than 10 and 100 μm (medians are indicated). Results of 8–24 wells per condition from five independent experiments are shown. Kruskal–Wallis test followed by Dunn post hoc test comparing transduced with untransduced cells. C, Migration of CMFDA-labeled UT (see also Supplementary Video S1) or MMP14 expressing (see also Supplementary Video S2) γδ T cells (green) in vibratome sections of viable BCSC5 xenograft tumors. Shown are representative Z-projections of confocal time-lapse videos from BCSC5 xenograft tumor slices stained for EpCAM (blue) and fibronectin (red) to identify tumor cell regions and stromal compartments, respectively. D, The mean speed of γδ T cells migrating in BCSC5 xenograft tumor slices is shown (left; Mann-Whitney test). The same data were analyzed with respect to the mean speed of γδ T cells in stromal ECM compartments (fibronectin+) and tumor cell regions (EpCAM+) of BCSC5 xenograft tumor slices (right; Kruskal-Wallis test followed by Dunn post hoc test comparing all groups against each other). E, The percentage of cells, which have been able to enter EpCAM+ tumor tissue (left) or which have resided over 50% of their monitored time inside EpCAM+ tumor tissue (right), was quantified in each time-lapse experiment (median, minimum to maximum). Unpaired t test, two tailed. D, Results from 15 (UT) and 11 (MMP14) time-lapse acquisitions from seven independent experiments are shown including at least 440 tracks per group. Outliers were identified and removed using the ROUT method (Q = 2%). *, P ≤ 0.05; **, P ≤ 0.01; ***, P ≤ 0.001. ECM, extracellular matrix; EpCAM, epithelial cellular adhesion molecule; UT, untransduced.
Figure 2 from Breast Cancer Stem Cell–Derived Tumors Escape from γδ T-cell Immunosurveillance In Vivo by Modulating γδ T-cell Ligands
Authors: Raute Katrin , Strietz Juliane , Parigiani Maria Alejandra , Andrieux Geoffroy , Thomas Oliver S. , Kistner Klaus M. , Zintchenko Marina , Aichele Peter , Hofmann Maike , Zhou Houjiang , Weber Wilfried , Boerries Melanie , Swamy Mahima , Maurer Jochen , Minguet Susana
Published: June 2023

Expanded γδ T cells migrate toward BCSC CM. A, Schematic transwell migration assay (left). Primary T cells were seeded in the wells of a permeable support with 5-μm pore size. The lower compartment was filled with BCSC CM and cells that transmigrated into the lower compartment were analyzed by flow cytometry. Statistical analysis of transmigrated γδ T cells (CD3+γδTCR+) is shown (right). Basal migration toward medium was set to 1.0 and fold changes from two independent experiments using 7 healthy donors in total were pooled (median, minimum to maximum). One-sample t test against hypothetical value of 1.0. B, Transwell assays were performed and analyzed as in A. Transmigrated Vδ1+ (CD3+γδTCR+Vδ1+) and Vδ2+ (CD3+γδTCR+Vδ2+) T cells were distinguished by flow cytometry. One-sample t test (for Vδ1+) or one-sample Wilcoxon test (for Vδ2+). C, Transwell assays were performed and analyzed as in A. Comparison of transmigrated αβ T cells (CD3+γδTCR−) and γδ T cells (CD3+γδTCR+; data from A) in response to BCSC5 CM. One sample t test against hypothetical value of 1.0. D, Representative chemokine receptor expression levels in αβ (CD3+γδTCR−), γδ (CD3+γδTCR+), Vδ1+ (CD3+γδTCR+Vδ1+), and Vδ2+ (CD3+γδTCR+Vδ2+) T cells. Shown are representative flow cytometry histograms from one healthy donor out of 3 healthy donors analyzed. E, Chemokine expression levels determined by quantitative mass spectrometry of BCSC5. Protein intensities (log2) of three replicates are shown (means ± SEM). *, P ≤ 0.05; **, P ≤ 0.01; ***, P ≤ 0.001.
Figure 3 from The Immunopeptidome from a Genomic Perspective: Establishing the Noncanonical Landscape of MHC Class I–Associated Peptides
Authors: Bedran Georges , Gasser Hans-Christof , Weke Kenneth , Wang Tongjie , Bedran Dominika , Laird Alexander , Battail Christophe , Zanzotto Fabio Massimo , Pesquita Catia , Axelson Håkan , Rajan Ajitha , Harrison David J. , Palkowski Aleksander , Pawlik Maciej , Parys Maciej , O'Neill J. Robert , Brennan Paul M. , Symeonides Stefan N. , Goodlett David R. , Litchfield Kevin , Fahraeus Robin , Hupp Ted R. , Kote Sachin , Alfaro Javier A.
Published: June 2023

Landscape of posttranslationally modified and ncMAPs. Open search: A, Overview of PTMs identified by open search (blue: spectra without PTMs, orange: spectra with a known UNIMOD PTM localized on a specific amino acid on the peptide. Green: The mass shift is localized, however the known PTM options do not fit the modified residue. Red: Otherwise). B, Most abundant “annotated PTMs” grouped by type. Second-round search: C, Fraction of canonical (dark gray) and noncanonical (light gray) MAPs in the immunopeptidome. D, Proportion of canonical (dark gray) and noncanonical (light gray) MAPs with/without PTMs. E, Fraction of binders versus nonbinders for both canonical and noncanonical MAPs using NetMHCpan 4.1.
Figure 1 from Breast Cancer Stem Cell–Derived Tumors Escape from γδ T-cell Immunosurveillance In Vivo by Modulating γδ T-cell Ligands
Authors: Raute Katrin , Strietz Juliane , Parigiani Maria Alejandra , Andrieux Geoffroy , Thomas Oliver S. , Kistner Klaus M. , Zintchenko Marina , Aichele Peter , Hofmann Maike , Zhou Houjiang , Weber Wilfried , Boerries Melanie , Swamy Mahima , Maurer Jochen , Minguet Susana
Published: June 2023

Expanded γδ T cells recognize and kill BCSCs in vitro. A,In vitro killing of luciferase-expressing BCSCs by γδ T cells after 8 hours at various effector to target (E:T) ratios. Results from two independent experiments with a total of 3 healthy donors (HD) of γδ T cells are shown (means ± SEM). B,In vitro killing of BCSCs by γδ T cells and MACS-separated Vδ1+ and Vδ2+ T cells performed as in A. Cells were cocultured at an E:T ratio of 10:1. Results from 3 healthy donors of γδ T cells are shown (means ± SEM). C, Flow cytometry-based analysis of degranulation by MACS-separated Vδ1+ or Vδ2+T cells in response to BCSC contact for 3 hours. Stimulation with anti-CD3 and anti-CD28 served as positive control. Representative dot plots (left) and statistical analysis (right) of the percentage of CD107a+Vδ1+ or CD107a+Vδ2+cells. Results from 2 healthy donors of γδ T cells obtained in three independent experiments were pooled (means ± SEM). Two-way ANOVA followed by Sidak post hoc test comparing stimulated or cocultured cells with the corresponding medium control. ****, P ≤ 0.0001. E:T, effector to target; HD, healthy donor; ns, nonsignificant.
Figure 2 from The Immunopeptidome from a Genomic Perspective: Establishing the Noncanonical Landscape of MHC Class I–Associated Peptides
Authors: Bedran Georges , Gasser Hans-Christof , Weke Kenneth , Wang Tongjie , Bedran Dominika , Laird Alexander , Battail Christophe , Zanzotto Fabio Massimo , Pesquita Catia , Axelson Håkan , Rajan Ajitha , Harrison David J. , Palkowski Aleksander , Pawlik Maciej , Parys Maciej , O'Neill J. Robert , Brennan Paul M. , Symeonides Stefan N. , Goodlett David R. , Litchfield Kevin , Fahraeus Robin , Hupp Ted R. , Kote Sachin , Alfaro Javier A.
Published: June 2023

COD-dipp: A new high-throughput pipeline for a deep interrogation of immunopeptidomic datasets. Samples are first analyzed with an open search strategy to detect the landscape of PTMs. An FLR for the PTMs and FDR of 1% are applied. Simultaneously, the samples are analyzed using a novel de novo approach to identify noncanonical peptides. The de novo strategy trains a model per sample using quality-controlled PSMs from the MS-GF+ search engine to learn the direct interpretation of sample-specific mass spectra. The MS-GF+ results are split into three groups: training and testing to tune the hyperparameters and account for overfitting, and a validation group to approximate the accuracy per sample. De novo predicted peptides with an accuracy of at least 90% are sequentially mapped against the Human proteome (HP) then a 3-frame translation (3FT) database of protein-coding genes (1 mismatch allowed between leucine/isoleucine, i.e., Xle). Predicted de novo peptides matching any known protein are labeled “canonical”. Peptides mapping to the 3FT database with at least 3 amino acids mismatches from any known protein sequence are labeled “noncanonical”. Finally, a second-round search is performed as a validation approach. Four of the most abundantly identified PTMs and a custom database consisting of ENSEMBL proteins and noncanonical peptides are considered. The resulting canonical and noncanonical peptides are controlled to an FDR of 1% and aligned to the hg38 human genome.
Figure 1 from The Immunopeptidome from a Genomic Perspective: Establishing the Noncanonical Landscape of MHC Class I–Associated Peptides
Authors: Bedran Georges , Gasser Hans-Christof , Weke Kenneth , Wang Tongjie , Bedran Dominika , Laird Alexander , Battail Christophe , Zanzotto Fabio Massimo , Pesquita Catia , Axelson Håkan , Rajan Ajitha , Harrison David J. , Palkowski Aleksander , Pawlik Maciej , Parys Maciej , O'Neill J. Robert , Brennan Paul M. , Symeonides Stefan N. , Goodlett David R. , Litchfield Kevin , Fahraeus Robin , Hupp Ted R. , Kote Sachin , Alfaro Javier A.
Published: June 2023

Infographics of immunopeptidomic datasets included in this study. A, Different types of cancer considered in this study with the number of samples and sample types per cancer type. B, Proportions of different MS instruments used in this study. C, Antibodies used for IP. D, Overall count of HLA alleles per HLA gene. E, Overall count of MS immunopeptidomic samples per HLA allele.
Supplementary Tables and Figures from Targeting the IL1β Pathway for Cancer Immunotherapy Remodels the Tumor Microenvironment and Enhances Antitumor Immune Responses
Authors: Diwanji Rohan , O'Brien Neil A. , Choi Jiyoung E. , Nguyen Beverly , Laszewski Tyler , Grauel Angelo L. , Yan Zheng , Xu Xin , Wu Jincheng , Ruddy David A. , Piquet Michelle , Pelletier Marc R. , Savchenko Alexander , Charette LaSalette , Rodrik-Outmezguine Vanessa , Baum Jason , Millholland John M. , Wong Connie C. , Martin Anne-Marie , Dranoff Glenn , Pruteanu-Malinici Iulian , Cremasco Viviana , Sabatos-Peyton Catherine , Jayaraman Pushpa
Published: June 2023

Supplementary tables S1-S5 and figures S1-S7
Supplementary Data from T Cells Expressing a Modified FcγRI Exert Antibody-Dependent Cytotoxicity and Overcome the Limitations of CAR T-cell Therapy against Solid Tumors
Authors: Rasoulouniriana Diana , Santana-Magal Nadine , Gutwillig Amit , Farhat-Younis Leen , Tal Lior , Amar Sarah , Milyavsky Michael , Muddineni Siva Sai Naga Anurag , Solomon Neta , Shpilt Hana , Dotan Shahar , Pilpel Noam , Waskow Claudia , Feinmesser Meora , Rider Peleg , Carmi Yaron
Published: June 2023

Supplementary tables and figures
Data from T Cells Expressing a Modified FcγRI Exert Antibody-Dependent Cytotoxicity and Overcome the Limitations of CAR T-cell Therapy against Solid Tumors
Authors: Rasoulouniriana Diana , Santana-Magal Nadine , Gutwillig Amit , Farhat-Younis Leen , Tal Lior , Amar Sarah , Milyavsky Michael , Muddineni Siva Sai Naga Anurag , Solomon Neta , Shpilt Hana , Dotan Shahar , Pilpel Noam , Waskow Claudia , Feinmesser Meora , Rider Peleg , Carmi Yaron
Published: June 2023

Abstract
The pioneering design of chimeric antigen receptor (CAR) T-cell therapy demonstrated the potential of reprogramming the immune system. Nonetheless, T-cell exhaustion, toxicity, and suppressive microenvironments limit their efficacy in solid tumors. We previously characterized a subset of tumor-infiltrating CD4+ T cells expressing the FcγRI receptor. Herein, we detail engineering of a receptor, based on the FcγRI structure, allowing T cells to target tumor cells using antibody intermediates. These T cells showed effective and specific cytotoxicity only when an appropriate antibody was added. Only target-bound antibodies activated these cells, while free antibodies were internalized without activation. Their cytotoxic activity was correlated to target protein density, therefore targeting tumor cells with high antigen density while sparing normal cells with low or no expression. This activation mechanism prevented premature exhaustion. Furthermore, during antibody-dependent cytotoxicity these cells secreted attenuated cytokine levels compared with CAR T cells, thereby enhancing their safety profile. These cells eradicated established melanomas, infiltrated the tumor microenvironment, and facilitated host immune cell recruitment in immunocompetent mice. In NOD/SCID gamma mice the cells infiltrate, persist, and eradicate tumors. As opposed to CAR T-cell therapies, which require changing the receptor across different types of cancer, our engineered T cells remain the same across tumor types, while only the injected antibody changes. Overall, we generated a highly flexible T-cell therapy capable of binding a wide range of tumor cells with high affinity, while preserving the cytotoxic specificity only to cells expressing high density of tumor-associated antigens and using a single manufacturing process.
Data from Anti–PD-1 and Extended Half-life IL2 Synergize for Treatment of Murine Glioblastoma Independent of Host MHC Class I Expression
Authors: Tritz Zachariah P. , Ayasoufi Katayoun , Wolf Delaney M. , Owens Carley A. , Malo Courtney S. , Himes Benjamin T. , Fain Cori E. , Goddery Emma N. , Yokanovich Lila T. , Jin Fang , Hansen Michael J. , Parney Ian F. , Wang Chensu , Moynihan Kelly D. , Irvine Darrell J. , Wittrup K. Dane , Diaz Marcano Rosa M. , Vile Richard G. , Johnson Aaron J.
Published: June 2023

Abstract
Glioblastoma (GBM) is the most common malignant brain tumor in adults, responsible for approximately 225,000 deaths per year. Despite preclinical successes, most interventions have failed to extend patient survival by more than a few months. Treatment with anti—programmed cell death protein 1 (anti–PD-1) immune checkpoint blockade (ICB) monotherapy has been beneficial for malignant tumors such as melanoma and lung cancers but has yet to be effectively employed in GBM. This study aimed to determine whether supplementing anti–PD-1 ICB with engineered extended half-life IL2, a potent lymphoproliferative cytokine, could improve outcomes. This combination therapy, subsequently referred to as enhanced checkpoint blockade (ECB), delivered intraperitoneally, reliably cures approximately 50% of C57BL/6 mice bearing orthotopic GL261 gliomas and extends median survival of the treated cohort. In the CT2A model, characterized as being resistant to CBI, ECB caused a decrease in CT2A tumor volume in half of measured animals similar to what was observed in GL261-bearing mice, promoting a trending survival increase. ECB generates robust immunologic responses, features of which include secondary lymphoid organ enlargement and increased activation status of both CD4 and CD8 T cells. This immunity is durable, with long-term ECB survivors able to resist GL261 rechallenge. Through employment of depletion strategies, ECB's efficacy was shown to be independent of host MHC class I–restricted antigen presentation but reliant on CD4 T cells. These results demonstrate ECB is efficacious against the GL261 glioma model through an MHC class I–independent mechanism and supporting further investigation into IL2-supplemented ICB therapies for tumors of the central nervous system.
Data from Breast Cancer Stem Cell–Derived Tumors Escape from γδ T-cell Immunosurveillance In Vivo by Modulating γδ T-cell Ligands
Authors: Raute Katrin , Strietz Juliane , Parigiani Maria Alejandra , Andrieux Geoffroy , Thomas Oliver S. , Kistner Klaus M. , Zintchenko Marina , Aichele Peter , Hofmann Maike , Zhou Houjiang , Weber Wilfried , Boerries Melanie , Swamy Mahima , Maurer Jochen , Minguet Susana
Published: June 2023

Abstract
There are no targeted therapies for patients with triple-negative breast cancer (TNBC). TNBC is enriched in breast cancer stem cells (BCSC), which play a key role in metastasis, chemoresistance, relapse, and mortality. γδ T cells hold great potential in immunotherapy against cancer and might provide an approach to therapeutically target TNBC. γδ T cells are commonly observed to infiltrate solid tumors and have an extensive repertoire of tumor-sensing mechanisms, recognizing stress-induced molecules and phosphoantigens (pAgs) on transformed cells. Herein, we show that patient-derived triple-negative BCSCs are efficiently recognized and killed by ex vivo expanded γδ T cells from healthy donors. Orthotopically xenografted BCSCs, however, were refractory to γδ T-cell immunotherapy. We unraveled concerted differentiation and immune escape mechanisms: xenografted BCSCs lost stemness, expression of γδ T-cell ligands, adhesion molecules, and pAgs, thereby evading immune recognition by γδ T cells. Indeed, neither promigratory engineered γδ T cells, nor anti–PD-1 checkpoint blockade, significantly prolonged overall survival of tumor-bearing mice. BCSC immune escape was independent of the immune pressure exerted by the γδ T cells and could be pharmacologically reverted by zoledronate or IFNα treatment. These results pave the way for novel combinatorial immunotherapies for TNBC.
O estabelecimento das formas poéticas na Rússia: as experiências de Trediakóvski, Kantemir e Lomonóssov
Authors: Frate Rafael
Published: June 2023

O presente artigo trata do estabelecimento da forma poética da literatura russa moderna. O artigo oferece um panorama aos debates e questões travados na primeira metade do Séc. XVIII e demonstra como a primeira geração da poesia russa optou pela adoção do sistema sílabo-tônico como previsto na Carta sobre as Regras de Versificação Russa de Mikhail Lomonóssov. Conjuntamente, as propostas anteriores para a padronização e prescrição da forma poética russa feitas pelo poeta Antiokh Kantemir e pelo poeta douto e tradutor Vassíli Trediakóvski serão investigadas de modo a oferecer em língua portuguesa um relato detalhado de tão importante momento literário para a Rússia.