To noninvasively capture such responses in the blood, we developed and benchmarked a high-throughput TCR profiling approach using plasma, optimized for the fragmented nature of cfDNA and the non-templated nature of rearranged TCRs. In theory, T-cells with the greatest turnover could best reflect pivotal immune dynamics from both circulating and tissue-derived compartments, including non-circulating tissue-resident memory T-cells (Trm). Current TCR profiling methods generally require invasive tissue biopsies that capture a single snapshot of immune activity or are limited by the sheer diversity of the circulating TCR repertoire. Ctr., Stanford, CAĨDepartment of Pediatrics, Division of Hematology and Oncology, Stanford University, Stanford, CAĩDepartment of Radiation Oncology, Stanford University Medical Center, Stanford, CAġ0Department of Medicine, Division of Oncology & Department of Dermatology, Stanford University School of Medicine, Stanford, CAġ1Department of Medicine, Divisions of Hematology & Oncology, Stanford University Medical Center, Stanford, CAīackground: Characterization of T-cell receptor (TCR) diversity and dynamics is increasingly critical to understanding therapeutic immune responses targeting tumors. Alizadeh, MD, PhD 11ġDepartment of Medicine, Divisions of Hematology & Oncology, Stanford University, Stanford, CAĢDepartment of Medicine, Division of Oncology, Stanford University Medical Center, Stanford, CAģDepartment of Medicine, Divisions of Hematology & Oncology, Stanford University Medical Center, Palo Alto, CAĤDivision of Blood and Marrow Transplantation, Stanford University, Stanford, CAĥDepartment of Medicine, Stanford University, StanfordĦDepartment of Dermatology, Stanford University School of Medicine, Stanford, CAħPathology and Medicine/Hematology, Stanford Univ. Miklos, MD, PhD 4, Maximilian Diehn, MD, PhD 9 *, Michael S. Kim, MD 6, James Zehnder, MD 7, Crystal L. Frank, MD, PhD 4, Stefan Alig, MD 1 *, George Duran, BA 5 *, Youn H. Kurtz, MD, PhD 1, Charles Macaulay, MSc, BA 3 *, Andrea Garofalo, BS, BA 1 *, Matthew J. ![]() Craig, MPhil 2, Brian Sworder, MD, PhD 1, David M.
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