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14 results on '"Kenna R. Leis"'

1. Figure S1 from Leukocyte Heterogeneity in Pancreatic Ductal Adenocarcinoma: Phenotypic and Spatial Features Associated with Clinical Outcome

Author

Lisa M. Coussens, Brian M. Wolpin, Jonathan A. Nowak, Motomi Mori, Byung S. Park, Rosalie C. Sears, Jeremy Goecks, Brett Sheppard, Elizabeth M. Jaffee, Robert H. Vonderheide, Margaret A. Tempero, Wesley Horton, Dove Keith, Jason Link, Douglas A. Rubinson, Thomas E. Clancy, Sara A. Väyrynen, Andressa Dias Costa, Padraic Robinson, Meghan B. Lavoie, William Larson, Kenna R. Leis, Alison Grossblatt-Wait, Samuel Hwang, Chen Yuan, Annacarolina da Silva, Vicente Morales-Oyarvide, Shamilene Sivagnanam, Courtney B. Betts, and Shannon M. Liudahl

Abstract

Figure S1 is related to Figure 1 and shows image cytometry gating strategies used in multiplex IHC analysis

Published
2023
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2. Figure S2 from Leukocyte Heterogeneity in Pancreatic Ductal Adenocarcinoma: Phenotypic and Spatial Features Associated with Clinical Outcome

Author

Lisa M. Coussens, Brian M. Wolpin, Jonathan A. Nowak, Motomi Mori, Byung S. Park, Rosalie C. Sears, Jeremy Goecks, Brett Sheppard, Elizabeth M. Jaffee, Robert H. Vonderheide, Margaret A. Tempero, Wesley Horton, Dove Keith, Jason Link, Douglas A. Rubinson, Thomas E. Clancy, Sara A. Väyrynen, Andressa Dias Costa, Padraic Robinson, Meghan B. Lavoie, William Larson, Kenna R. Leis, Alison Grossblatt-Wait, Samuel Hwang, Chen Yuan, Annacarolina da Silva, Vicente Morales-Oyarvide, Shamilene Sivagnanam, Courtney B. Betts, and Shannon M. Liudahl

Abstract

Figure S2 is related to Figure 2 and contains data from global unsupervised clustering analysis of treatment naive PDACs. Data include cell densities of leukocyte subpopulations by cluster, quantification of tissue area evaluated in patients within each cluster, and t-SNE representations showing leukocyte density within regions of interest.

Published
2023
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3. Supplementary Data from Leukocyte Heterogeneity in Pancreatic Ductal Adenocarcinoma: Phenotypic and Spatial Features Associated with Clinical Outcome

Author

Lisa M. Coussens, Brian M. Wolpin, Jonathan A. Nowak, Motomi Mori, Byung S. Park, Rosalie C. Sears, Jeremy Goecks, Brett Sheppard, Elizabeth M. Jaffee, Robert H. Vonderheide, Margaret A. Tempero, Wesley Horton, Dove Keith, Jason Link, Douglas A. Rubinson, Thomas E. Clancy, Sara A. Väyrynen, Andressa Dias Costa, Padraic Robinson, Meghan B. Lavoie, William Larson, Kenna R. Leis, Alison Grossblatt-Wait, Samuel Hwang, Chen Yuan, Annacarolina da Silva, Vicente Morales-Oyarvide, Shamilene Sivagnanam, Courtney B. Betts, and Shannon M. Liudahl

Abstract

File contains supplementary Materials & Methods, supplementary References, and Supplementary Tables S1-S10.

Published
2023
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4. Figure S7 from Leukocyte Heterogeneity in Pancreatic Ductal Adenocarcinoma: Phenotypic and Spatial Features Associated with Clinical Outcome

Author

Lisa M. Coussens, Brian M. Wolpin, Jonathan A. Nowak, Motomi Mori, Byung S. Park, Rosalie C. Sears, Jeremy Goecks, Brett Sheppard, Elizabeth M. Jaffee, Robert H. Vonderheide, Margaret A. Tempero, Wesley Horton, Dove Keith, Jason Link, Douglas A. Rubinson, Thomas E. Clancy, Sara A. Väyrynen, Andressa Dias Costa, Padraic Robinson, Meghan B. Lavoie, William Larson, Kenna R. Leis, Alison Grossblatt-Wait, Samuel Hwang, Chen Yuan, Annacarolina da Silva, Vicente Morales-Oyarvide, Shamilene Sivagnanam, Courtney B. Betts, and Shannon M. Liudahl

Abstract

Figure S7 is related to Figure 7. It shows leukocyte features of primary PDACs receiving presurgical chemotherapy and/or radiotherapy, and leukocyte profiles of PDAC metastases

Published
2023
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5. Supplementary Data from Innate αβ T Cells Mediate Antitumor Immunity by Orchestrating Immunogenic Macrophage Programming

Author

George Miller, Lisa M. Coussens, Kwok-Kin Wong, Deepak Saxena, Varshini Vasudevaraja, Smruti Pushalkar, Dennis O. Adeegbe, Suhagi Shah, Jingjing Wu, Benjamin Wadowski, Mohammad Saad Farooq, Kathryn Chin, Justin Lish, Maeliss Gelas, Muhammad Israr, Salma Adam, Brian Diskin, Joshua Leinwand, Berk Aykut, Wei Wang, Shivraj Savadkar, Igor Dolgalev, K.M. Sadeq Islam, Jeremy Goecks, Shamilene Sivagnanam, Rosalie C. Sears, Jason Link, Adesola Ogunsakin, Luisana E. Torres, Mirhee Kim, Harshita Mehrotra, Kenna R. Leis, Shannon M. Liudahl, Juan Andres Kochen Rossi, Ankita Mishra, Emma Kurz, and Mautin Hundeyin

Abstract

Supp Figures 1-7 and Legends

Published
2023
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6. Data from Innate αβ T Cells Mediate Antitumor Immunity by Orchestrating Immunogenic Macrophage Programming

Author

George Miller, Lisa M. Coussens, Kwok-Kin Wong, Deepak Saxena, Varshini Vasudevaraja, Smruti Pushalkar, Dennis O. Adeegbe, Suhagi Shah, Jingjing Wu, Benjamin Wadowski, Mohammad Saad Farooq, Kathryn Chin, Justin Lish, Maeliss Gelas, Muhammad Israr, Salma Adam, Brian Diskin, Joshua Leinwand, Berk Aykut, Wei Wang, Shivraj Savadkar, Igor Dolgalev, K.M. Sadeq Islam, Jeremy Goecks, Shamilene Sivagnanam, Rosalie C. Sears, Jason Link, Adesola Ogunsakin, Luisana E. Torres, Mirhee Kim, Harshita Mehrotra, Kenna R. Leis, Shannon M. Liudahl, Juan Andres Kochen Rossi, Ankita Mishra, Emma Kurz, and Mautin Hundeyin

Abstract

Unconventional T-lymphocyte populations are emerging as important regulators of tumor immunity. Despite this, the role of TCRαβ+CD4−CD8−NK1.1− innate αβ T cells (iαβT) in pancreatic ductal adenocarcinoma (PDA) has not been explored. We found that iαβTs represent ∼10% of T lymphocytes infiltrating PDA in mice and humans. Intratumoral iαβTs express a distinct T-cell receptor repertoire and profoundly immunogenic phenotype compared with their peripheral counterparts and conventional lymphocytes. iαβTs comprised ∼75% of the total intratumoral IL17+ cells. Moreover, iαβT-cell adoptive transfer is protective in both murine models of PDA and human organotypic systems. We show that iαβT cells induce a CCR5-dependent immunogenic macrophage reprogramming, thereby enabling marked CD4+ and CD8+ T-cell expansion/activation and tumor protection. Collectively, iαβTs govern fundamental intratumoral cross-talk between innate and adaptive immune populations and are attractive therapeutic targets.Significance:We found that iαβTs are a profoundly activated T-cell subset in PDA that slow tumor growth in murine and human models of disease. iαβTs induce a CCR5-dependent immunogenic tumor-associated macrophage program, T-cell activation and expansion, and should be considered as novel targets for immunotherapy.See related commentary by Banerjee et al., p. 1164.This article is highlighted in the In This Issue feature, p. 1143

Published
2023
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7. Figure S6 from Leukocyte Heterogeneity in Pancreatic Ductal Adenocarcinoma: Phenotypic and Spatial Features Associated with Clinical Outcome

Author

Lisa M. Coussens, Brian M. Wolpin, Jonathan A. Nowak, Motomi Mori, Byung S. Park, Rosalie C. Sears, Jeremy Goecks, Brett Sheppard, Elizabeth M. Jaffee, Robert H. Vonderheide, Margaret A. Tempero, Wesley Horton, Dove Keith, Jason Link, Douglas A. Rubinson, Thomas E. Clancy, Sara A. Väyrynen, Andressa Dias Costa, Padraic Robinson, Meghan B. Lavoie, William Larson, Kenna R. Leis, Alison Grossblatt-Wait, Samuel Hwang, Chen Yuan, Annacarolina da Silva, Vicente Morales-Oyarvide, Shamilene Sivagnanam, Courtney B. Betts, and Shannon M. Liudahl

Abstract

Figure S6 is related to Figure 6. It shows leukocyte densities and phenotypes in treatment-naive short-term versus long-term survivors

Published
2023
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8. Figure S3 from Leukocyte Heterogeneity in Pancreatic Ductal Adenocarcinoma: Phenotypic and Spatial Features Associated with Clinical Outcome

Author

Lisa M. Coussens, Brian M. Wolpin, Jonathan A. Nowak, Motomi Mori, Byung S. Park, Rosalie C. Sears, Jeremy Goecks, Brett Sheppard, Elizabeth M. Jaffee, Robert H. Vonderheide, Margaret A. Tempero, Wesley Horton, Dove Keith, Jason Link, Douglas A. Rubinson, Thomas E. Clancy, Sara A. Väyrynen, Andressa Dias Costa, Padraic Robinson, Meghan B. Lavoie, William Larson, Kenna R. Leis, Alison Grossblatt-Wait, Samuel Hwang, Chen Yuan, Annacarolina da Silva, Vicente Morales-Oyarvide, Shamilene Sivagnanam, Courtney B. Betts, and Shannon M. Liudahl

Abstract

Figure S3 is related to Figure 3 and shows comparisons of leukocyte densities between treatment-naive PDACS from Cohort 1 and Cohort 2, shows leukocyte subpopulations whose density most strongly correlates to total leukocyte density within PDACs, and shows patient overall survival based on total leukocyte density in tumor and adjacent stroma.

Published
2023
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9. Figure S5 from Leukocyte Heterogeneity in Pancreatic Ductal Adenocarcinoma: Phenotypic and Spatial Features Associated with Clinical Outcome

Author

Lisa M. Coussens, Brian M. Wolpin, Jonathan A. Nowak, Motomi Mori, Byung S. Park, Rosalie C. Sears, Jeremy Goecks, Brett Sheppard, Elizabeth M. Jaffee, Robert H. Vonderheide, Margaret A. Tempero, Wesley Horton, Dove Keith, Jason Link, Douglas A. Rubinson, Thomas E. Clancy, Sara A. Väyrynen, Andressa Dias Costa, Padraic Robinson, Meghan B. Lavoie, William Larson, Kenna R. Leis, Alison Grossblatt-Wait, Samuel Hwang, Chen Yuan, Annacarolina da Silva, Vicente Morales-Oyarvide, Shamilene Sivagnanam, Courtney B. Betts, and Shannon M. Liudahl

Abstract

Figure S5 is related to Figure 5. It shows multiple metrics of intrapatient heterogeneity based on size and histopathology type of assessed tissue.

Published
2023
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10. Figure S4 from Leukocyte Heterogeneity in Pancreatic Ductal Adenocarcinoma: Phenotypic and Spatial Features Associated with Clinical Outcome

Author

Lisa M. Coussens, Brian M. Wolpin, Jonathan A. Nowak, Motomi Mori, Byung S. Park, Rosalie C. Sears, Jeremy Goecks, Brett Sheppard, Elizabeth M. Jaffee, Robert H. Vonderheide, Margaret A. Tempero, Wesley Horton, Dove Keith, Jason Link, Douglas A. Rubinson, Thomas E. Clancy, Sara A. Väyrynen, Andressa Dias Costa, Padraic Robinson, Meghan B. Lavoie, William Larson, Kenna R. Leis, Alison Grossblatt-Wait, Samuel Hwang, Chen Yuan, Annacarolina da Silva, Vicente Morales-Oyarvide, Shamilene Sivagnanam, Courtney B. Betts, and Shannon M. Liudahl

Abstract

Figure S4 is related to Figure 4. It shows leukocyte composition based on tumor grade, molecular status, and histopathologic region.

Published
2023
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11. Supp Table 1 from Innate αβ T Cells Mediate Antitumor Immunity by Orchestrating Immunogenic Macrophage Programming

Author

George Miller, Lisa M. Coussens, Kwok-Kin Wong, Deepak Saxena, Varshini Vasudevaraja, Smruti Pushalkar, Dennis O. Adeegbe, Suhagi Shah, Jingjing Wu, Benjamin Wadowski, Mohammad Saad Farooq, Kathryn Chin, Justin Lish, Maeliss Gelas, Muhammad Israr, Salma Adam, Brian Diskin, Joshua Leinwand, Berk Aykut, Wei Wang, Shivraj Savadkar, Igor Dolgalev, K.M. Sadeq Islam, Jeremy Goecks, Shamilene Sivagnanam, Rosalie C. Sears, Jason Link, Adesola Ogunsakin, Luisana E. Torres, Mirhee Kim, Harshita Mehrotra, Kenna R. Leis, Shannon M. Liudahl, Juan Andres Kochen Rossi, Ankita Mishra, Emma Kurz, and Mautin Hundeyin

Abstract

Supp Table 1

Published
2023
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12. Leukocyte Heterogeneity in Pancreatic Ductal Adenocarcinoma: Phenotypic and Spatial Features Associated with Clinical Outcome

Author

Thomas E. Clancy, Jeremy Goecks, Dove Keith, Brian M. Wolpin, Vicente Morales-Oyarvide, Annacarolina da Silva, Andressa Dias Costa, Samuel Hwang, Meghan B. Lavoie, William Larson, Sara A. Väyrynen, Shannon M. Liudahl, Jason Link, Lisa M. Coussens, Kenna R. Leis, Byung Park, Courtney Betts, Margaret A. Tempero, Elizabeth M. Jaffee, Motomi Mori, Douglas A. Rubinson, Padraic Robinson, Robert H. Vonderheide, Alison Grossblatt-Wait, Wesley Horton, Rosalie C. Sears, Jonathan A. Nowak, Brett C. Sheppard, Shamilene Sivagnanam, and Chen Yuan

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, Myeloid, Pancreatic ductal adenocarcinoma, endocrine system diseases, T cell, In silico, Article, 03 medical and health sciences, 0302 clinical medicine, Immune system, Internal medicine, Biopsy, Leukocytes, Tumor Microenvironment, medicine, Humans, Tissue microarray, medicine.diagnostic_test, business.industry, Phenotype, digestive system diseases, Pancreatic Neoplasms, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Immunotherapy, business, Carcinoma, Pancreatic Ductal
Abstract

Immunotherapies targeting aspects of T cell functionality are efficacious in many solid tumors, but pancreatic ductal adenocarcinoma (PDAC) remains refractory to these treatments. Deeper understanding of the PDAC immune ecosystem is needed to identify additional therapeutic targets and predictive biomarkers for therapeutic response and resistance monitoring. To address these needs, we quantitatively evaluated leukocyte contexture in 135 human PDACs at single-cell resolution by profiling density and spatial distribution of myeloid and lymphoid cells within histopathologically defined regions of surgical resections from treatment-naive and presurgically (neoadjuvant)–treated patients and biopsy specimens from metastatic PDAC. Resultant data establish an immune atlas of PDAC heterogeneity, identify leukocyte features correlating with clinical outcomes, and, through an in silico study, provide guidance for use of PDAC tissue microarrays to optimally measure intratumoral immune heterogeneity. Atlas data have direct applicability as a reference for evaluating immune responses to investigational neoadjuvant PDAC therapeutics where pretherapy baseline specimens are not available. Significance: We provide a phenotypic and spatial immune atlas of human PDAC identifying leukocyte composition at steady state and following standard neoadjuvant therapies. These data have broad utility as a resource that can inform on leukocyte responses to emerging therapies where baseline tissues were not acquired. This article is highlighted in the In This Issue feature, p. 1861

Published
2021
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13. Tumor-Infiltrating Leukocyte Phenotypes Distinguish Outcomes in Related Patients With Pancreatic Adenocarcinoma

Author

Kenna R. Leis, Mary McDonnell, Terry K. Morgan, Jason Link, Kelly Hamman, Brett Johnson, Lisa M. Coussens, Carl Pelz, Jone E. Sampson, Charles D. Lopez, Dove Keith, Rosalie C. Sears, Shamilene Sivagnanam, Courtney Betts, and Shannon M. Liudahl

Subjects
Adult, Cancer Research, business.industry, MEDLINE, CASE REPORTS, Adenocarcinoma, Middle Aged, medicine.disease, Phenotype, Pancreatic Neoplasms, Text mining, Treatment Outcome, Oncology, Cancer research, Leukocytes, Medicine, Humans, Translational Oncology, business
Published
2021

14. Innate αβ T cells Mediate Anti-tumor Immunity by Orchestrating Immunogenic Macrophage Programming

Author

Deepak Saxena, Kwok-Kin Wong, Brian Diskin, George Miller, Berk Aykut, Varshini Vasudevaraja, Dennis Adeegbe, Shannon M. Liudahl, Wei Wang, Salma Adam, Mautin Hundeyin, Maeliss Gelas, Smruti Pushalkar, Kenna R. Leis, Jason Link, Kathryn Chin, Emma Kurz, Shivraj Savadkar, Rosalie C. Sears, Jingjing Wu, Joshua Leinwand, Harshita Mehrotra, Jeremy Goecks, K. M.Sadeq Islam, Benjamin Wadowski, Justin Lish, Luisana E. Torres, Adesola Ogunsakin, Lisa M. Coussens, Igor Dolgalev, Juan A. Kochen Rossi, Ankita Mishra, Mohammad Saad Farooq, Mirhee Kim, Suhagi Shah, Muhammad Israr, and Shamilene Sivagnanam

Subjects
0301 basic medicine, Male, Adoptive cell transfer, medicine.medical_treatment, T cell, Receptors, Antigen, T-Cell, alpha-beta, T-Lymphocytes, Biology, Immunotherapy, Adoptive, Article, 03 medical and health sciences, Mice, 0302 clinical medicine, Immune system, Antigen, Cell Line, Tumor, medicine, Tumor Microenvironment, Macrophage, Animals, Humans, Tumor microenvironment, Macrophages, Immunotherapy, Immunity, Innate, Mice, Inbred C57BL, Pancreatic Neoplasms, 030104 developmental biology, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Cancer research, Female, CD8, Neoplasm Transplantation, Carcinoma, Pancreatic Ductal
Abstract

Unconventional T-lymphocyte populations are emerging as important regulators of tumor immunity. Despite this, the role of TCRαβ+CD4−CD8−NK1.1− innate αβ T cells (iαβT) in pancreatic ductal adenocarcinoma (PDA) has not been explored. We found that iαβTs represent ∼10% of T lymphocytes infiltrating PDA in mice and humans. Intratumoral iαβTs express a distinct T-cell receptor repertoire and profoundly immunogenic phenotype compared with their peripheral counterparts and conventional lymphocytes. iαβTs comprised ∼75% of the total intratumoral IL17+ cells. Moreover, iαβT-cell adoptive transfer is protective in both murine models of PDA and human organotypic systems. We show that iαβT cells induce a CCR5-dependent immunogenic macrophage reprogramming, thereby enabling marked CD4+ and CD8+ T-cell expansion/activation and tumor protection. Collectively, iαβTs govern fundamental intratumoral cross-talk between innate and adaptive immune populations and are attractive therapeutic targets. Significance: We found that iαβTs are a profoundly activated T-cell subset in PDA that slow tumor growth in murine and human models of disease. iαβTs induce a CCR5-dependent immunogenic tumor-associated macrophage program, T-cell activation and expansion, and should be considered as novel targets for immunotherapy. See related commentary by Banerjee et al., p. 1164. This article is highlighted in the In This Issue feature, p. 1143

Published
2019

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