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244 results on '"Yusko, Erik"'

1. Multimodal, broadly neutralizing antibodies against SARS-CoV-2 identified by high-throughput native pairing of BCRs from bulk B cells

Author

Keitany, Gladys J., Rubin, Benjamin E.R., Garrett, Meghan E., Musa, Andrea, Tracy, Jeff, Liang, Yu, Ebert, Peter, Moore, Amanda J., Guan, Jonathan, Eggers, Erica, Lescano, Ninnia, Brown, Ryan, Carbo, Adria, Al-Asadi, Hussein, Ching, Travers, Day, Austin, Harris, Rebecca, Linkem, Charles, Popov, Dimitry, Wilkins, Courtney, Li, Lianqu, Wang, Jiao, Liu, Chuanxin, Chen, Li, Dines, Jennifer N., Atyeo, Caroline, Alter, Galit, Baldo, Lance, Sherwood, Anna, Howie, Bryan, Klinger, Mark, Yusko, Erik, Robins, Harlan S., Benzeno, Sharon, and Gilbert, Amy E.

Published
2023
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2. Bivalent intra-spike binding provides durability against emergent Omicron lineages: Results from a global consortium

Author

Callaway, Heather M., Hastie, Kathryn M., Schendel, Sharon L., Li, Haoyang, Yu, Xiaoying, Shek, Jeremy, Buck, Tierra, Hui, Sean, Bedinger, Dan, Troup, Camille, Dennison, S. Moses, Li, Kan, Alpert, Michael D., Bailey, Charles C., Benzeno, Sharon, Bonnevier, Jody L., Chen, Jin-Qiu, Chen, Charm, Cho, Hyeseon, Crompton, Peter D., Dussupt, Vincent, Entzminger, Kevin C., Ezzyat, Yassine, Fleming, Jonathan K., Geukens, Nick, Gilbert, Amy E., Guan, Yongjun, Han, Xiaojian, Harvey, Christopher J., Hatler, Julia M., Howie, Bryan, Hu, Chao, Huang, Ailong, Imbrechts, Maya, Jin, Aishun, Kamachi, Nik, Keitany, Gladys, Klinger, Mark, Kolls, Jay K., Krebs, Shelly J., Li, Tingting, Luo, Feiyan, Maruyama, Toshiaki, Meehl, Michael A., Mendez-Rivera, Letzibeth, Musa, Andrea, Okumura, C.J., Rubin, Benjamin E.R., Sato, Aaron K., Shen, Meiying, Singh, Anirudh, Song, Shuyi, Tan, Joshua, Trimarchi, Jeffrey M., Upadhyay, Dhruvkumar P., Wang, Yingming, Yu, Lei, Yuan, Tom Z., Yusko, Erik, Peters, Bjoern, Tomaras, Georgia, and Saphire, Erica Ollmann

Published
2023
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5. Ibrutinib Therapy Increases T Cell Repertoire Diversity in Patients with Chronic Lymphocytic Leukemia

Author

Yin, Qingsong, Sivina, Mariela, Robins, Harlan, Yusko, Erik, Vignali, Marissa, O'Brien, Susan, Keating, Michael J, Ferrajoli, Alessandra, Estrov, Zeev, Jain, Nitin, Wierda, William G, and Burger, Jan A

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Rare Diseases, Orphan Drug, Clinical Trials and Supportive Activities, Hematology, Clinical Research, Cancer, Lymphoma, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Adenine, Aged, B-Lymphocytes, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cytokines, High-Throughput Nucleotide Sequencing, Humans, Leukemia, Lymphocytic, Chronic, B-Cell, Piperidines, Protein-Tyrosine Kinases, Pyrazoles, Pyrimidines, Biochemistry and cell biology
Abstract

The Bruton's tyrosine kinase inhibitor ibrutinib is a highly effective, new targeted therapy for chronic lymphocytic leukemia (CLL) that thwarts leukemia cell survival, growth, and tissue homing. The effects of ibrutinib treatment on the T cell compartment, which is clonally expanded and thought to support the growth of malignant B cells in CLL, are not fully characterized. Using next-generation sequencing technology, we characterized the diversity of TCRβ-chains in peripheral blood T cells from 15 CLL patients before and after 1 y of ibrutinib therapy. We noted elevated CD4+ and CD8+ T cell numbers and a restricted TCRβ repertoire in all pretreatment samples. After 1 y of ibrutinib therapy, elevated peripheral blood T cell numbers and T cell-related cytokine levels had normalized, and T cell repertoire diversity increased significantly. Dominant TCRβ clones in pretreatment samples declined or became undetectable, and the number of productive unique clones increased significantly during ibrutinib therapy, with the emergence of large numbers of low-frequency TCRβ clones. Importantly, broader TCR repertoire diversity was associated with clinical efficacy and lower rates of infections during ibrutinib therapy. These data demonstrate that ibrutinib therapy increases diversification of the T cell compartment in CLL patients, which contributes to cellular immune reconstitution.

Published
2017

6. Real-time shape approximation and 5-D fingerprinting of single proteins

Author

Yusko, Erik C., Bruhn, Brandon R., Eggenberger, Olivia, Houghtaling, Jared, Rollings, Ryan C., Walsh, Nathan C., Nandivada, Santoshi, Pindrus, Mariya, Hall, Adam R., Sept, David, Li, Jiali, Kalonia, Devendra S., and Mayer, Michael

Subjects
Quantitative Biology - Biomolecules, Condensed Matter - Soft Condensed Matter, Physics - Biological Physics
Abstract

This work exploits the zeptoliter sensing volume of electrolyte-filled nanopores to determine, simultaneously and in real time, the approximate shape, volume, charge, rotational diffusion coefficient, and dipole moment of individual proteins. We have developed the theory for a quantitative understanding and analysis of modulations in ionic current that arise from rotational dynamics of single proteins as they move through the electric field inside a nanopore. The resulting multi-parametric information raises the possibility to characterize, identify, and quantify individual proteins and protein complexes in a mixture. This approach interrogates single proteins in solution and determines parameters such as the approximate shape and dipole moment, which are excellent protein descriptors and cannot be obtained otherwise from single protein molecules in solution. Taken together, this five-dimensional characterization of biomolecules at the single particle level has the potential for instantaneous protein identification, quantification, and possibly sorting with implications for structural biology, proteomics, biomarker detection, and routine protein analysis.

Published
2015
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8. TCR Sequencing Can Identify and Track Glioma-Infiltrating T Cells after DC Vaccination

Author

Hsu, Melody, Sedighim, Shaina, Wang, Tina, Antonios, Joseph P, Everson, Richard G, Tucker, Alexander M, Du, Lin, Emerson, Ryan, Yusko, Erik, Sanders, Catherine, Robins, Harlan S, Yong, William H, Davidson, Tom B, Li, Gang, Liau, Linda M, and Prins, Robert M

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Brain Disorders, Rare Diseases, Immunotherapy, Neurosciences, Cancer, Brain Cancer, Biotechnology, Immunization, Orphan Drug, Vaccine Related, Clinical Research, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Good Health and Well Being, Brain Neoplasms, Dendritic Cells, Disease Progression, Glioblastoma, Humans, Immunotherapy, Adoptive, Lymphocytes, Tumor-Infiltrating, Receptors, Antigen, T-Cell, Survival Analysis, Vaccination, Pharmacology and Pharmaceutical Sciences, Oncology and carcinogenesis
Abstract

Although immunotherapeutic strategies are emerging as adjunctive treatments for cancer, sensitive methods of monitoring the immune response after treatment remain to be established. We used a novel next-generation sequencing approach to determine whether quantitative assessments of tumor-infiltrating lymphocyte (TIL) content and the degree of overlap of T-cell receptor (TCR) sequences in brain tumors and peripheral blood were predictors of immune response and overall survival in glioblastoma patients treated with autologous tumor lysate-pulsed dendritic cell immunotherapy. A statistically significant correlation was found between a higher estimated TIL content and increased time to progression and overall survival. In addition, we were able to assess the proportion of shared TCR sequences between tumor and peripheral blood at time points before and after therapy, and found the level of TCR overlap to correlate with survival outcomes. Higher degrees of overlap, or the development of an increased overlap following immunotherapy, was correlated with improved clinical outcome, and may provide insights into the successful, antigen-specific immune response. Cancer Immunol Res; 4(5); 412-8. ©2016 AACR.

Published
2016

11. Comprehensive T cell repertoire characterization of non-small cell lung cancer

Author

Reuben, Alexandre, Zhang, Jiexin, Chiou, Shin-Heng, Gittelman, Rachel M., Li, Jun, Lee, Won-Chul, Fujimoto, Junya, Behrens, Carmen, Liu, Xiaoke, Wang, Feng, Quek, Kelly, Wang, Chunlin, Kheradmand, Farrah, Chen, Runzhe, Chow, Chi-Wan, Lin, Heather, Bernatchez, Chantale, Jalali, Ali, Hu, Xin, Wu, Chang-Jiun, Eterovic, Agda Karina, Parra, Edwin Roger, Yusko, Erik, Emerson, Ryan, Benzeno, Sharon, Vignali, Marissa, Wu, Xifeng, Ye, Yuanqing, Little, Latasha D., Gumbs, Curtis, Mao, Xizeng, Song, Xingzhi, Tippen, Samantha, Thornton, Rebecca L., Cascone, Tina, Snyder, Alexandra, Wargo, Jennifer A., Herbst, Roy, Swisher, Stephen, Kadara, Humam, Moran, Cesar, Kalhor, Neda, Zhang, Jianhua, Scheet, Paul, Vaporciyan, Ara A., Sepesi, Boris, Gibbons, Don L., Robins, Harlan, Hwu, Patrick, Heymach, John V., Sharma, Padmanee, Allison, James P., Baladandayuthapani, Veera, Lee, Jack J., Davis, Mark M., Wistuba, Ignacio I., Futreal, P. Andrew, and Zhang, Jianjun

Published
2020
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12. Data from TCR Sequencing Can Identify and Track Glioma-Infiltrating T Cells after DC Vaccination

Author

Hsu, Melody S., primary, Sedighim, Shaina, primary, Wang, Tina, primary, Antonios, Joseph P., primary, Everson, Richard G., primary, Tucker, Alexander M., primary, Du, Lin, primary, Emerson, Ryan, primary, Yusko, Erik, primary, Sanders, Catherine, primary, Robins, Harlan S., primary, Yong, William H., primary, Davidson, Tom B., primary, Li, Gang, primary, Liau, Linda M., primary, and Prins, Robert M., primary

Published
2023
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13. Supplementary Table 2 from TCR Sequencing Can Identify and Track Glioma-Infiltrating T Cells after DC Vaccination

Author

Hsu, Melody S., primary, Sedighim, Shaina, primary, Wang, Tina, primary, Antonios, Joseph P., primary, Everson, Richard G., primary, Tucker, Alexander M., primary, Du, Lin, primary, Emerson, Ryan, primary, Yusko, Erik, primary, Sanders, Catherine, primary, Robins, Harlan S., primary, Yong, William H., primary, Davidson, Tom B., primary, Li, Gang, primary, Liau, Linda M., primary, and Prins, Robert M., primary

Published
2023
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14. Supplementary Table 1 from TCR Sequencing Can Identify and Track Glioma-Infiltrating T Cells after DC Vaccination

Author

Hsu, Melody S., primary, Sedighim, Shaina, primary, Wang, Tina, primary, Antonios, Joseph P., primary, Everson, Richard G., primary, Tucker, Alexander M., primary, Du, Lin, primary, Emerson, Ryan, primary, Yusko, Erik, primary, Sanders, Catherine, primary, Robins, Harlan S., primary, Yong, William H., primary, Davidson, Tom B., primary, Li, Gang, primary, Liau, Linda M., primary, and Prins, Robert M., primary

Published
2023
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15. Supplementary Table 3 from TCR Sequencing Can Identify and Track Glioma-Infiltrating T Cells after DC Vaccination

Author

Hsu, Melody S., primary, Sedighim, Shaina, primary, Wang, Tina, primary, Antonios, Joseph P., primary, Everson, Richard G., primary, Tucker, Alexander M., primary, Du, Lin, primary, Emerson, Ryan, primary, Yusko, Erik, primary, Sanders, Catherine, primary, Robins, Harlan S., primary, Yong, William H., primary, Davidson, Tom B., primary, Li, Gang, primary, Liau, Linda M., primary, and Prins, Robert M., primary

Published
2023
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16. Data from TCR Repertoire Intratumor Heterogeneity in Localized Lung Adenocarcinomas: An Association with Predicted Neoantigen Heterogeneity and Postsurgical Recurrence

Author

Reuben, Alexandre, primary, Gittelman, Rachel, primary, Gao, Jianjun, primary, Zhang, Jiexin, primary, Yusko, Erik C., primary, Wu, Chang-Jiun, primary, Emerson, Ryan, primary, Zhang, Jianhua, primary, Tipton, Christopher, primary, Li, Jun, primary, Quek, Kelly, primary, Gopalakrishnan, Vancheswaran, primary, Chen, Runzhe, primary, Vence, Luis M., primary, Cascone, Tina, primary, Vignali, Marissa, primary, Fujimoto, Junya, primary, Rodriguez-Canales, Jaime, primary, Parra, Edwin R., primary, Little, Latasha D., primary, Gumbs, Curtis, primary, Forget, Marie-Andrée, primary, Federico, Lorenzo, primary, Haymaker, Cara, primary, Behrens, Carmen, primary, Benzeno, Sharon, primary, Bernatchez, Chantale, primary, Sepesi, Boris, primary, Gibbons, Don L., primary, Wargo, Jennifer A., primary, William, William N., primary, Swisher, Stephen, primary, Heymach, John V., primary, Robins, Harlan, primary, Lee, J. Jack, primary, Sharma, Padmanee, primary, Allison, James P., primary, Futreal, P. Andrew, primary, Wistuba, Ignacio I., primary, and Zhang, Jianjun, primary

Published
2023
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17. Supplementary Figure S2 from Concurrent PD-1 Blockade Negates the Effects of OX40 Agonist Antibody in Combination Immunotherapy through Inducing T-cell Apoptosis

Author

Shrimali, Rajeev K., primary, Ahmad, Shamim, primary, Verma, Vivek, primary, Zeng, Peng, primary, Ananth, Sudha, primary, Gaur, Pankaj, primary, Gittelman, Rachel M., primary, Yusko, Erik, primary, Sanders, Catherine, primary, Robins, Harlan, primary, Hammond, Scott A., primary, Janik, John E., primary, Mkrtichyan, Mikayel, primary, Gupta, Seema, primary, and Khleif, Samir N., primary

Published
2023
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18. Supplementary Figure 1 from TCR Sequencing Can Identify and Track Glioma-Infiltrating T Cells after DC Vaccination

Author

Hsu, Melody S., primary, Sedighim, Shaina, primary, Wang, Tina, primary, Antonios, Joseph P., primary, Everson, Richard G., primary, Tucker, Alexander M., primary, Du, Lin, primary, Emerson, Ryan, primary, Yusko, Erik, primary, Sanders, Catherine, primary, Robins, Harlan S., primary, Yong, William H., primary, Davidson, Tom B., primary, Li, Gang, primary, Liau, Linda M., primary, and Prins, Robert M., primary

Published
2023
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19. Supplementary Figure 3 from TCR Sequencing Can Identify and Track Glioma-Infiltrating T Cells after DC Vaccination

Author

Hsu, Melody S., primary, Sedighim, Shaina, primary, Wang, Tina, primary, Antonios, Joseph P., primary, Everson, Richard G., primary, Tucker, Alexander M., primary, Du, Lin, primary, Emerson, Ryan, primary, Yusko, Erik, primary, Sanders, Catherine, primary, Robins, Harlan S., primary, Yong, William H., primary, Davidson, Tom B., primary, Li, Gang, primary, Liau, Linda M., primary, and Prins, Robert M., primary

Published
2023
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20. Supplementary Figure Legends from Concurrent PD-1 Blockade Negates the Effects of OX40 Agonist Antibody in Combination Immunotherapy through Inducing T-cell Apoptosis

Author

Shrimali, Rajeev K., primary, Ahmad, Shamim, primary, Verma, Vivek, primary, Zeng, Peng, primary, Ananth, Sudha, primary, Gaur, Pankaj, primary, Gittelman, Rachel M., primary, Yusko, Erik, primary, Sanders, Catherine, primary, Robins, Harlan, primary, Hammond, Scott A., primary, Janik, John E., primary, Mkrtichyan, Mikayel, primary, Gupta, Seema, primary, and Khleif, Samir N., primary

Published
2023
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21. Supplementary Tables 1 through 3 and Supplementary Figures 1 through 4 from Targeted Next Generation Sequencing Identifies Markers of Response to PD-1 Blockade

Author

Johnson, Douglas B., primary, Frampton, Garrett M., primary, Rioth, Matthew J., primary, Yusko, Erik, primary, Xu, Yaomin, primary, Guo, Xingyi, primary, Ennis, Riley C., primary, Fabrizio, David, primary, Chalmers, Zachary R., primary, Greenbowe, Joel, primary, Ali, Siraj M., primary, Balasubramanian, Sohail, primary, Sun, James X., primary, He, Yuting, primary, Frederick, Dennie T., primary, Puzanov, Igor, primary, Balko, Justin M., primary, Cates, Justin M., primary, Ross, Jeffrey S., primary, Sanders, Catherine, primary, Robins, Harlan, primary, Shyr, Yu, primary, Miller, Vincent A., primary, Stephens, Philip J., primary, Sullivan, Ryan J., primary, Sosman, Jeffrey A., primary, and Lovly, Christine M., primary

Published
2023
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22. Supplemental Table from TCR Repertoire Intratumor Heterogeneity in Localized Lung Adenocarcinomas: An Association with Predicted Neoantigen Heterogeneity and Postsurgical Recurrence

Author

Reuben, Alexandre, primary, Gittelman, Rachel, primary, Gao, Jianjun, primary, Zhang, Jiexin, primary, Yusko, Erik C., primary, Wu, Chang-Jiun, primary, Emerson, Ryan, primary, Zhang, Jianhua, primary, Tipton, Christopher, primary, Li, Jun, primary, Quek, Kelly, primary, Gopalakrishnan, Vancheswaran, primary, Chen, Runzhe, primary, Vence, Luis M., primary, Cascone, Tina, primary, Vignali, Marissa, primary, Fujimoto, Junya, primary, Rodriguez-Canales, Jaime, primary, Parra, Edwin R., primary, Little, Latasha D., primary, Gumbs, Curtis, primary, Forget, Marie-Andrée, primary, Federico, Lorenzo, primary, Haymaker, Cara, primary, Behrens, Carmen, primary, Benzeno, Sharon, primary, Bernatchez, Chantale, primary, Sepesi, Boris, primary, Gibbons, Don L., primary, Wargo, Jennifer A., primary, William, William N., primary, Swisher, Stephen, primary, Heymach, John V., primary, Robins, Harlan, primary, Lee, J. Jack, primary, Sharma, Padmanee, primary, Allison, James P., primary, Futreal, P. Andrew, primary, Wistuba, Ignacio I., primary, and Zhang, Jianjun, primary

Published
2023
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23. Supplementary Figure 2 from TCR Sequencing Can Identify and Track Glioma-Infiltrating T Cells after DC Vaccination

Author

Hsu, Melody S., primary, Sedighim, Shaina, primary, Wang, Tina, primary, Antonios, Joseph P., primary, Everson, Richard G., primary, Tucker, Alexander M., primary, Du, Lin, primary, Emerson, Ryan, primary, Yusko, Erik, primary, Sanders, Catherine, primary, Robins, Harlan S., primary, Yong, William H., primary, Davidson, Tom B., primary, Li, Gang, primary, Liau, Linda M., primary, and Prins, Robert M., primary

Published
2023
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25. Data from Concurrent PD-1 Blockade Negates the Effects of OX40 Agonist Antibody in Combination Immunotherapy through Inducing T-cell Apoptosis

Author

Shrimali, Rajeev K., primary, Ahmad, Shamim, primary, Verma, Vivek, primary, Zeng, Peng, primary, Ananth, Sudha, primary, Gaur, Pankaj, primary, Gittelman, Rachel M., primary, Yusko, Erik, primary, Sanders, Catherine, primary, Robins, Harlan, primary, Hammond, Scott A., primary, Janik, John E., primary, Mkrtichyan, Mikayel, primary, Gupta, Seema, primary, and Khleif, Samir N., primary

Published
2023
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26. Supplemental Figure Legends from TCR Repertoire Intratumor Heterogeneity in Localized Lung Adenocarcinomas: An Association with Predicted Neoantigen Heterogeneity and Postsurgical Recurrence

Author

Reuben, Alexandre, primary, Gittelman, Rachel, primary, Gao, Jianjun, primary, Zhang, Jiexin, primary, Yusko, Erik C., primary, Wu, Chang-Jiun, primary, Emerson, Ryan, primary, Zhang, Jianhua, primary, Tipton, Christopher, primary, Li, Jun, primary, Quek, Kelly, primary, Gopalakrishnan, Vancheswaran, primary, Chen, Runzhe, primary, Vence, Luis M., primary, Cascone, Tina, primary, Vignali, Marissa, primary, Fujimoto, Junya, primary, Rodriguez-Canales, Jaime, primary, Parra, Edwin R., primary, Little, Latasha D., primary, Gumbs, Curtis, primary, Forget, Marie-Andrée, primary, Federico, Lorenzo, primary, Haymaker, Cara, primary, Behrens, Carmen, primary, Benzeno, Sharon, primary, Bernatchez, Chantale, primary, Sepesi, Boris, primary, Gibbons, Don L., primary, Wargo, Jennifer A., primary, William, William N., primary, Swisher, Stephen, primary, Heymach, John V., primary, Robins, Harlan, primary, Lee, J. Jack, primary, Sharma, Padmanee, primary, Allison, James P., primary, Futreal, P. Andrew, primary, Wistuba, Ignacio I., primary, and Zhang, Jianjun, primary

Published
2023
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27. Data from Targeted Next Generation Sequencing Identifies Markers of Response to PD-1 Blockade

Author

Johnson, Douglas B., primary, Frampton, Garrett M., primary, Rioth, Matthew J., primary, Yusko, Erik, primary, Xu, Yaomin, primary, Guo, Xingyi, primary, Ennis, Riley C., primary, Fabrizio, David, primary, Chalmers, Zachary R., primary, Greenbowe, Joel, primary, Ali, Siraj M., primary, Balasubramanian, Sohail, primary, Sun, James X., primary, He, Yuting, primary, Frederick, Dennie T., primary, Puzanov, Igor, primary, Balko, Justin M., primary, Cates, Justin M., primary, Ross, Jeffrey S., primary, Sanders, Catherine, primary, Robins, Harlan, primary, Shyr, Yu, primary, Miller, Vincent A., primary, Stephens, Philip J., primary, Sullivan, Ryan J., primary, Sosman, Jeffrey A., primary, and Lovly, Christine M., primary

Published
2023
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29. Supplemental Figures S1-S11 from TCR Repertoire Intratumor Heterogeneity in Localized Lung Adenocarcinomas: An Association with Predicted Neoantigen Heterogeneity and Postsurgical Recurrence

Author

Reuben, Alexandre, primary, Gittelman, Rachel, primary, Gao, Jianjun, primary, Zhang, Jiexin, primary, Yusko, Erik C., primary, Wu, Chang-Jiun, primary, Emerson, Ryan, primary, Zhang, Jianhua, primary, Tipton, Christopher, primary, Li, Jun, primary, Quek, Kelly, primary, Gopalakrishnan, Vancheswaran, primary, Chen, Runzhe, primary, Vence, Luis M., primary, Cascone, Tina, primary, Vignali, Marissa, primary, Fujimoto, Junya, primary, Rodriguez-Canales, Jaime, primary, Parra, Edwin R., primary, Little, Latasha D., primary, Gumbs, Curtis, primary, Forget, Marie-Andrée, primary, Federico, Lorenzo, primary, Haymaker, Cara, primary, Behrens, Carmen, primary, Benzeno, Sharon, primary, Bernatchez, Chantale, primary, Sepesi, Boris, primary, Gibbons, Don L., primary, Wargo, Jennifer A., primary, William, William N., primary, Swisher, Stephen, primary, Heymach, John V., primary, Robins, Harlan, primary, Lee, J. Jack, primary, Sharma, Padmanee, primary, Allison, James P., primary, Futreal, P. Andrew, primary, Wistuba, Ignacio I., primary, and Zhang, Jianjun, primary

Published
2023
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30. Supplemental Figure 4 from Fractionated Radiation Therapy Stimulates Antitumor Immunity Mediated by Both Resident and Infiltrating Polyclonal T-cell Populations when Combined with PD-1 Blockade

Author

Dovedi, Simon J., primary, Cheadle, Eleanor J., primary, Popple, Amy L., primary, Poon, Edmund, primary, Morrow, Michelle, primary, Stewart, Ross, primary, Yusko, Erik C., primary, Sanders, Catherine M., primary, Vignali, Marissa, primary, Emerson, Ryan O., primary, Robins, Harlan S., primary, Wilkinson, Robert W., primary, Honeychurch, Jamie, primary, and Illidge, Timothy M., primary

Published
2023
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31. Supplemental Figure 1 from Fractionated Radiation Therapy Stimulates Antitumor Immunity Mediated by Both Resident and Infiltrating Polyclonal T-cell Populations when Combined with PD-1 Blockade

Author

Dovedi, Simon J., primary, Cheadle, Eleanor J., primary, Popple, Amy L., primary, Poon, Edmund, primary, Morrow, Michelle, primary, Stewart, Ross, primary, Yusko, Erik C., primary, Sanders, Catherine M., primary, Vignali, Marissa, primary, Emerson, Ryan O., primary, Robins, Harlan S., primary, Wilkinson, Robert W., primary, Honeychurch, Jamie, primary, and Illidge, Timothy M., primary

Published
2023
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32. Supplemental Figure Legends from Fractionated Radiation Therapy Stimulates Antitumor Immunity Mediated by Both Resident and Infiltrating Polyclonal T-cell Populations when Combined with PD-1 Blockade

Author

Dovedi, Simon J., primary, Cheadle, Eleanor J., primary, Popple, Amy L., primary, Poon, Edmund, primary, Morrow, Michelle, primary, Stewart, Ross, primary, Yusko, Erik C., primary, Sanders, Catherine M., primary, Vignali, Marissa, primary, Emerson, Ryan O., primary, Robins, Harlan S., primary, Wilkinson, Robert W., primary, Honeychurch, Jamie, primary, and Illidge, Timothy M., primary

Published
2023
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33. Supplemental Figure 6 from Fractionated Radiation Therapy Stimulates Antitumor Immunity Mediated by Both Resident and Infiltrating Polyclonal T-cell Populations when Combined with PD-1 Blockade

Author

Dovedi, Simon J., primary, Cheadle, Eleanor J., primary, Popple, Amy L., primary, Poon, Edmund, primary, Morrow, Michelle, primary, Stewart, Ross, primary, Yusko, Erik C., primary, Sanders, Catherine M., primary, Vignali, Marissa, primary, Emerson, Ryan O., primary, Robins, Harlan S., primary, Wilkinson, Robert W., primary, Honeychurch, Jamie, primary, and Illidge, Timothy M., primary

Published
2023
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34. Supplemental Figure 5 from Fractionated Radiation Therapy Stimulates Antitumor Immunity Mediated by Both Resident and Infiltrating Polyclonal T-cell Populations when Combined with PD-1 Blockade

Author

Dovedi, Simon J., primary, Cheadle, Eleanor J., primary, Popple, Amy L., primary, Poon, Edmund, primary, Morrow, Michelle, primary, Stewart, Ross, primary, Yusko, Erik C., primary, Sanders, Catherine M., primary, Vignali, Marissa, primary, Emerson, Ryan O., primary, Robins, Harlan S., primary, Wilkinson, Robert W., primary, Honeychurch, Jamie, primary, and Illidge, Timothy M., primary

Published
2023
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35. Supplemental Figure 3 from Fractionated Radiation Therapy Stimulates Antitumor Immunity Mediated by Both Resident and Infiltrating Polyclonal T-cell Populations when Combined with PD-1 Blockade

Author

Dovedi, Simon J., primary, Cheadle, Eleanor J., primary, Popple, Amy L., primary, Poon, Edmund, primary, Morrow, Michelle, primary, Stewart, Ross, primary, Yusko, Erik C., primary, Sanders, Catherine M., primary, Vignali, Marissa, primary, Emerson, Ryan O., primary, Robins, Harlan S., primary, Wilkinson, Robert W., primary, Honeychurch, Jamie, primary, and Illidge, Timothy M., primary

Published
2023
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36. Supplemental Figure 2 from Fractionated Radiation Therapy Stimulates Antitumor Immunity Mediated by Both Resident and Infiltrating Polyclonal T-cell Populations when Combined with PD-1 Blockade

Author

Dovedi, Simon J., primary, Cheadle, Eleanor J., primary, Popple, Amy L., primary, Poon, Edmund, primary, Morrow, Michelle, primary, Stewart, Ross, primary, Yusko, Erik C., primary, Sanders, Catherine M., primary, Vignali, Marissa, primary, Emerson, Ryan O., primary, Robins, Harlan S., primary, Wilkinson, Robert W., primary, Honeychurch, Jamie, primary, and Illidge, Timothy M., primary

Published
2023
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42. Contribution of systemic and somatic factors to clinical response and resistance to PD-L1 blockade in urothelial cancer: An exploratory multi-omic analysis

Author

Snyder, Alexandra, Nathanson, Tavi, Funt, Samuel A., Ahuja, Arun, Buros Novik, Jacqueline, Hellmann, Matthew D., Chang, Eliza, Aksoy, Bulent Arman, Al-Ahmadie, Hikmat, Yusko, Erik, Vignali, Marissa, Benzeno, Sharon, Boyd, Mariel, Moran, Meredith, Iyer, Gopa, Robins, Harlan S., Mardis, Elaine R., Merghoub, Taha, Hammerbacher, Jeff, Rosenberg, Jonathan E., and Bajorin, Dean F.

Subjects
Atezolizumab -- Dosage and administration, Cancer -- Care and treatment, Urothelium -- Research, Membrane proteins -- Research, Biological sciences
Abstract

Background Inhibition of programmed death-ligand 1 (PD-L1) with atezolizumab can induce durable clinical benefit (DCB) in patients with metastatic urothelial cancers, including complete remissions in patients with chemotherapy refractory disease. Although mutation load and PD-L1 immune cell (IC) staining have been associated with response, they lack sufficient sensitivity and specificity for clinical use. Thus, there is a need to evaluate the peripheral blood immune environment and to conduct detailed analyses of mutation load, predicted neoantigens, and immune cellular infiltration in tumors to enhance our understanding of the biologic underpinnings of response and resistance. Methods and findings The goals of this study were to (1) evaluate the association of mutation load and predicted neoantigen load with therapeutic benefit and (2) determine whether intratumoral and peripheral blood T cell receptor (TCR) clonality inform clinical outcomes in urothelial carcinoma treated with atezolizumab. We hypothesized that an elevated mutation load in combination with T cell clonal dominance among intratumoral lymphocytes prior to treatment or among peripheral T cells after treatment would be associated with effective tumor control upon treatment with anti-PD-L1 therapy. We performed whole exome sequencing (WES), RNA sequencing (RNA-seq), and T cell receptor sequencing (TCR-seq) of pretreatment tumor samples as well as TCR-seq of matched, serially collected peripheral blood, collected before and after treatment with atezolizumab. These parameters were assessed for correlation with DCB (defined as progression-free survival [PFS] >6 months), PFS, and overall survival (OS), both alone and in the context of clinical and intratumoral parameters known to be predictive of survival in this disease state. Patients with DCB displayed a higher proportion of tumor-infiltrating T lymphocytes (TIL) (n = 24, Mann-Whitney p = 0.047). Pretreatment peripheral blood TCR clonality below the median was associated with improved PFS (n = 29, log-rank p = 0.048) and OS (n = 29, log-rank p = 0.011). Patients with DCB also demonstrated more substantial expansion of tumor-associated TCR clones in the peripheral blood 3 weeks after starting treatment (n = 22, Mann-Whitney p = 0.022). The combination of high pretreatment peripheral blood TCR clonality with elevated PD-L1 IC staining in tumor tissue was strongly associated with poor clinical outcomes (n = 10, hazard ratio (HR) (mean) = 89.88, HR (median) = 23.41, 95% CI [2.43, 506.94], p(HR > 1) = 0.0014). Marked variations in mutation loads were seen with different somatic variant calling methodologies, which, in turn, impacted associations with clinical outcomes. Missense mutation load, predicted neoantigen load, and expressed neoantigen load did not demonstrate significant association with DCB (n = 25, Mann-Whitney p = 0.22, n = 25, Mann-Whitney p = 0.55, and n = 25, Mann-Whitney p = 0.29, respectively). Instead, we found evidence of time-varying effects of somatic mutation load on PFS in this cohort (n = 25, p = 0.044). A limitation of our study is its small sample size (n = 29), a subset of the patients treated on IMvigor 210 (NCT02108652). Given the number of exploratory analyses performed, we intend for these results to be hypothesis-generating. Conclusions These results demonstrate the complex nature of immune response to checkpoint blockade and the compelling need for greater interrogation and data integration of both host and tumor factors. Incorporating these variables in prospective studies will facilitate identification and treatment of resistant patients., Author(s): Alexandra Snyder 1,2,*, Tavi Nathanson 3, Samuel A. Funt 1,2, Arun Ahuja 3, Jacqueline Buros Novik 3, Matthew D. Hellmann 1,2, Eliza Chang 3, Bulent Arman Aksoy 3, Hikmat [...]

Published
2017
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44. Additional file 1: of Neoadjuvant ipilimumab (3 mg/kg or 10 mg/kg) and high dose IFN-α2b in locally/regionally advanced melanoma: safety, efficacy and impact on T-cell repertoire

Author

Tarhini, Ahmad, Lin, Yan, Lin, Huang, Rahman, Zahra, Vallabhaneni, Priyanka, Prateek Mendiratta, Pingpank, James, Holtzman, Matthew, Yusko, Erik, Rytlewski, Julie, Rao, Uma, Ferris, Robert, and Kirkwood, John

Abstract

Figure S4. Clonal relatedness in the tumor and blood. The number of tumor-associated clones in the baseline tumor biopsies that were expanded in blood post-treatment was strongly correlated with both (A) tumor infiltrating lymphocyte (TIL) fraction (Rho 0.7299, p = 0.0003) and (B) TIL clone diversity (Rho 0.882, p = 2.7− 7). (PPTX 338 kb)

Published
2018
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45. T Cell Repertoire Dynamics during Pregnancy in Multiple Sclerosis

Author

Ramien, Caren, primary, Yusko, Erik C., additional, Engler, Jan Broder, additional, Gamradt, Stefanie, additional, Patas, Kostas, additional, Schweingruber, Nils, additional, Willing, Anne, additional, Rosenkranz, Sina Cathérine, additional, Diemert, Anke, additional, Harrison, Anja, additional, Vignali, Marissa, additional, Sanders, Catherine, additional, Robins, Harlan S., additional, Tolosa, Eva, additional, Heesen, Christoph, additional, Arck, Petra C., additional, Scheffold, Alexander, additional, Chan, Kenneth, additional, Emerson, Ryan O., additional, Friese, Manuel A., additional, and Gold, Stefan M., additional

Published
2019
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47. Abstract CT077: Potential utility of minimal residual disease (MRD) to identify relapse in pediatric and young adult (AYA) B-cell acute lymphoblastic leukemia (B-ALL) patients treated with tisagenlecleucel

Author

Pulsipher, Michael A., primary, Han, Xia, additional, Quigley, Máire, additional, Kari, Gabor, additional, Rives, Susana, additional, Laetsch, Theodore W., additional, Myers, Gary D., additional, Hiramatsu, Hidefumi, additional, Yanik, Gregory A., additional, Qayed, Muna, additional, Driscoll, Timothy, additional, Boyer, Michael W., additional, Stefanski, Heather, additional, Buchner, Jochen, additional, Baruchel, Andre, additional, Bader, Peter, additional, Yi, Lan, additional, Kalfoglou, Creton, additional, Robins, Harlan, additional, Yusko, Erik, additional, Gorgun, Gullu, additional, Bleickardt, Eric, additional, Wong, Stephane, additional, and Grupp, Stephan A., additional

Published
2019
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49. High frequency of HER2-specific immunity observed in patients (pts) with HER2+ cancers treated with margetuximab (M), an Fc-enhanced anti-HER2 monoclonal antibody (mAb).

Author

Nordstrom, Jeffrey L., primary, Muth, John, additional, Erskine, Courtney L., additional, Sanders, Catherine, additional, Yusko, Erik C., additional, Emerson, Ryan O, additional, Lee, Min-Jung, additional, Lee, Sunmin, additional, Trepel, Jane B, additional, Im, Seock-Ah, additional, Bang, Yung-Jue, additional, Giaccone, Giuseppe, additional, Bauer, Todd Michael, additional, Burris, Howard A., additional, Baughman, Jan E., additional, Rock, Edwin P., additional, Moore, Paul A., additional, Bonvini, Ezio, additional, and Knutson, Keith L, additional

Published
2019
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