Research

Our research focuses the dissection of mechanisms that underlie response and resistance to immunotherapies and on the longitudinal tracking of tumor cell evolution using single-cell lineage-tracing approaches based on interrogation of natural barcodes like somatic nuclear or mitochondrial DNA mutations.

Highlighted

Tracking rare single donor and recipient immune and leukemia cells after allogeneic hematopoietic cell transplantation using mitochondrial DNA mutations

Livius Penter, Nicoletta Cieri, Katie Maurer, Marwan Kwok, Haoxiang Lyu, ..., Gad Getz, Jacqueline S. Garcia, Robert J. Soiffer, Kenneth J. Livak, Catherine J. Wu

Blood Cancer Discovery   ·   05 Sep 2024   ·   doi:10.1158/2643-3230.BCD-23-0138

Single-cell tracking of clonal evolution and microchimerism using mitochondrial DNA mutations

single cell genomics stem cell transplantation clonal evolution

Integrative genotyping of cancer and immune phenotypes by long-read sequencing

Livius Penter, Mehdi Borji, Adi Nagler, Haoxiang Lyu, Wesley S. Lu, ..., Jerome Ritz, Robert J. Soiffer, Jacqueline S. Garcia, Kenneth J. Livak, Catherine J. Wu

Nature Communications   ·   02 Jan 2024   ·   doi:10.1038/s41467-023-44137-7

Targeted genotyping of scRNA-seq cDNA libraries using long-read sequencing with Oxford Nanopore

nanoranger scRNA-seq targeted genotyping long-read sequencing ONT

Mechanisms of response and resistance to combined decitabine and ipilimumab for advanced myeloid disease

Livius Penter, Yang Liu, Jacquelyn O. Wolff, Lin Yang, Len Taing, ..., Jennifer Altreuter, Franziska Michor, Robert J. Soiffer, Jacqueline S. Garcia, Catherine J. Wu

Blood   ·   13 Apr 2023   ·   doi:10.1182/blood.2022018246

Single cell RNA sequencing analysis dissecting responses to ipilimumab treatment of relapsed AML/MDS with and without stem cell transplantation.

scRNA-seq AML immunotherapy stem cell transplantation

Longitudinal Single-Cell Dynamics of Chromatin Accessibility and Mitochondrial Mutations in Chronic Lymphocytic Leukemia Mirror Disease History

Livius Penter, Satyen H. Gohil, Caleb Lareau, Leif S. Ludwig, Erin M. Parry, ..., Matthew S. Davids, Donna S. Neuberg, Kenneth J. Livak, Vijay G. Sankaran, Catherine J. Wu

Cancer Discovery   ·   01 Dec 2021   ·   doi:10.1158/2159-8290.CD-21-0276

First demonstration that longitudinal changes of mitochondrial DNA mutations reflect therapeutic bottlenecks.

mtDNA mutations lineage-tracing CLL clonal evolution

All

2024

Therapy response in AML: a tale of two T cells

Livius Penter, Catherine J. Wu

Blood   ·   12 Sep 2024   ·   doi:10.1182/blood.2024024593

Commentary on Mazziotta et al

single cell genomics AML editorial

Tracking rare single donor and recipient immune and leukemia cells after allogeneic hematopoietic cell transplantation using mitochondrial DNA mutations

Livius Penter, Nicoletta Cieri, Katie Maurer, Marwan Kwok, Haoxiang Lyu, ..., Gad Getz, Jacqueline S. Garcia, Robert J. Soiffer, Kenneth J. Livak, Catherine J. Wu

Blood Cancer Discovery   ·   05 Sep 2024   ·   doi:10.1158/2643-3230.BCD-23-0138

Single-cell tracking of clonal evolution and microchimerism using mitochondrial DNA mutations

single cell genomics stem cell transplantation clonal evolution

A multidimensional analysis reveals distinct immune phenotypes and the composition of immune aggregates in pediatric acute myeloid leukemia

Joost B. Koedijk, Inge van der Werf, Livius Penter, Marijn A. Vermeulen, Farnaz Barneh, ..., Henrik Hasle, Stefan Nierkens, Mirjam E. Belderbos, C. Michel Zwaan, Olaf Heidenreich

Leukemia   ·   26 Aug 2024   ·   doi:10.1038/s41375-024-02381-w

Immune cell networks in pediatric and adult acute myeloid leukemia

spatial analysis immunotherapy AML

Artifacts in single-cell mitochondrial DNA mutation analyses misinform phylogenetic inference

Caleb A. Lareau, Michael S. Chapman, Livius Penter, Tal Nawy, Dana Pe’er, Leif S. Ludwig

Cold Spring Harbor Laboratory   ·   29 Jul 2024   ·   doi:10.1101/2024.07.28.605517

Commentary on problematic analyses of mitochondrial DNA mutations

single cell genomics mitochondrial DNA mutations editorial

Oncogene-induced TIM-3 ligand expression dictates susceptibility to anti–TIM-3 therapy in mice

Nana Talvard-Balland, Lukas M. Braun, Karen O. Dixon, Melissa Zwick, Helena Engel, ..., Burkhard Becher, Natalie Köhler, Tobias Wertheimer, Vijay K. Kuchroo, Robert Zeiser

Journal of Clinical Investigation   ·   25 Jun 2024   ·   doi:10.1172/JCI177460

TIM-3 inhibition stimulates graft-versus-leukemia responses against AML

immunotherapy AML

Single-cell genomics-based immune and disease monitoring in blood malignancies

Anja C. Rathgeber, Leif S. Ludwig, Livius Penter

Clinical Hematology International   ·   14 Jun 2024   ·   doi:10.46989/001c.117961

Single-cell genomics-based immune and disease monitoring in blood malignancies

single cell genomics immune monitoring clonal evolution review

Integrative genotyping of cancer and immune phenotypes by long-read sequencing

Livius Penter, Mehdi Borji, Adi Nagler, Haoxiang Lyu, Wesley S. Lu, ..., Jerome Ritz, Robert J. Soiffer, Jacqueline S. Garcia, Kenneth J. Livak, Catherine J. Wu

Nature Communications   ·   02 Jan 2024   ·   doi:10.1038/s41467-023-44137-7

Targeted genotyping of scRNA-seq cDNA libraries using long-read sequencing with Oxford Nanopore

nanoranger scRNA-seq targeted genotyping long-read sequencing ONT

2023

Preexisting tumor-resident T cells with cytotoxic potential associate with response to neoadjuvant anti–PD-1 in head and neck cancer

Giacomo Oliveira, Ann Marie Egloff, Alexander B. Afeyan, Jacquelyn O. Wolff, Zexiang Zeng, ..., Dorina Kallogjeri, Jay F. Piccirillo, Douglas R. Adkins, Catherine J. Wu, Ravindra Uppaluri

Science Immunology   ·   29 Sep 2023   ·   doi:10.1126/sciimmunol.adf4968

First demonstration that preexisting tumor-resident T cells associate with response to neoadjuvant anti-PD-1 in head and neck cancer

scRNA-seq PD-1 immunotherapy tumor immunology

Mechanisms of response and resistance to combined decitabine and ipilimumab for advanced myeloid disease

Livius Penter, Yang Liu, Jacquelyn O. Wolff, Lin Yang, Len Taing, ..., Jennifer Altreuter, Franziska Michor, Robert J. Soiffer, Jacqueline S. Garcia, Catherine J. Wu

Blood   ·   13 Apr 2023   ·   doi:10.1182/blood.2022018246

Single cell RNA sequencing analysis dissecting responses to ipilimumab treatment of relapsed AML/MDS with and without stem cell transplantation.

scRNA-seq AML immunotherapy stem cell transplantation

Ipilimumab plus decitabine for patients with MDS or AML in posttransplant or transplant-naïve settings

Jacqueline S. Garcia, Yael Flamand, Livius Penter, Michael Keng, Benjamin K. Tomlinson, ..., Catherine J. Wu, Daniel J. DeAngelo, Donna Neuberg, Richard M. Stone, Robert J. Soiffer

Blood   ·   13 Apr 2023   ·   doi:10.1182/blood.2022017686

Clinical study of CTLA-4 blockade and decitabine in relapsed AML/MDS with or without stem cell transplantation.

AML MDS CTLA-4 blockade stem cell transplantation

2022

In VivoModeling of CLL Transformation to Richter Syndrome Reveals Convergent Evolutionary Paths and Therapeutic Vulnerabilities

Elisa ten Hacken, Tomasz Sewastianik, Shanye Yin, Gabriela Brunsting Hoffmann, Michaela Gruber, ..., Kenneth J. Livak, Ivana Bozic, Donna S. Neuberg, Ruben D. Carrasco, Catherine J. Wu

Blood Cancer Discovery   ·   06 Dec 2022   ·   doi:10.1158/2643-3230.BCD-22-0082

Mitochondrial DNA Mutations as Natural Barcodes for Lineage Tracing of Murine Tumor Models

Livius Penter, Elisa ten Hacken, Jackson Southard, Caleb A. Lareau, Leif S. Ludwig, Shuqiang Li, Donna S. Neuberg, Kenneth J. Livak, Catherine J. Wu

Cancer Research   ·   05 Dec 2022   ·   doi:10.1158/0008-5472.CAN-22-0275

First demonstration of mtDNA mutation-based lineage-tracing in murine cancer models.

CLL mtDNA mutations lineage-tracing

Immune Phenotypes and Target Antigens of Clonally Expanded Bone Marrow T Cells in Treatment-Naïve Multiple Myeloma

Carlotta Welters, María Fernanda Lammoglia Cobo, Christian Alexander Stein, Meng-Tung Hsu, Amin Ben Hamza, ..., Holger Hackstein, Hans-Peter Rahn, Klaus Dornmair, Thomas Blankenstein, Leo Hansmann

Cancer Immunology Research   ·   19 Sep 2022   ·   doi:10.1158/2326-6066.CIR-22-0434

AML relapse after a TIGIT race

Livius Penter, Catherine J. Wu

Blood   ·   15 Sep 2022   ·   doi:10.1182/blood.2022017614

Comment on Gournay et al. describing post-transplant immune reconstitution dynamics.

Rapid single-cell identification of Epstein–Barr virus-specific T-cell receptors for cellular therapy

María Fernanda Lammoglia Cobo, Carlotta Welters, Leonie Rosenberger, Matthias Leisegang, Kerstin Dietze, ..., Klaus Dornmair, Thomas Blankenstein, Thomas Kammertöns, Armin Gerbitz, Leo Hansmann

Cytotherapy   ·   01 Aug 2022   ·   doi:10.1016/j.jcyt.2022.03.005

Improved T-cell Immunity Following Neoadjuvant Chemotherapy in Ovarian Cancer

Min Liu, Nabihah Tayob, Livius Penter, MacLean Sellars, Anna Tarren, ..., Guanglan Zhang, Ursula A. Matulonis, Catherine J. Wu, Derin B. Keskin, Panagiotis A. Konstantinopoulos

Clinical Cancer Research   ·   20 Apr 2022   ·   doi:10.1158/1078-0432.CCR-21-2834

Natural Barcodes for Longitudinal Single Cell Tracking of Leukemic and Immune Cell Dynamics

Livius Penter, Satyen H. Gohil, Catherine J. Wu

Frontiers in Immunology   ·   03 Jan 2022   ·   doi:10.3389/fimmu.2021.788891

2021

Longitudinal Single-Cell Dynamics of Chromatin Accessibility and Mitochondrial Mutations in Chronic Lymphocytic Leukemia Mirror Disease History

Livius Penter, Satyen H. Gohil, Caleb Lareau, Leif S. Ludwig, Erin M. Parry, ..., Matthew S. Davids, Donna S. Neuberg, Kenneth J. Livak, Vijay G. Sankaran, Catherine J. Wu

Cancer Discovery   ·   01 Dec 2021   ·   doi:10.1158/2159-8290.CD-21-0276

First demonstration that longitudinal changes of mitochondrial DNA mutations reflect therapeutic bottlenecks.

mtDNA mutations lineage-tracing CLL clonal evolution

Coevolving JAK2V617F+relapsed AML and donor T cells with PD-1 blockade after stem cell transplantation: an index case

Livius Penter, Satyen H. Gohil, Teddy Huang, Emily M. Thrash, Dominik Schmidt, ..., F. Stephen Hodi, Kenneth J. Livak, Robert Zeiser, Pavan Bachireddy, Catherine J. Wu

Blood Advances   ·   18 Nov 2021   ·   doi:10.1182/bloodadvances.2021004335

Integrated analysis of exceptional response to PD-1 inhibition in relapsed sAML after allogeneic stem cell transplantation with scRNA-seq, CITE-seq, scATAC-seq and CyTOF.

Molecular and cellular features of CTLA-4 blockade for relapsed myeloid malignancies after transplantation

Livius Penter, Yi Zhang, Alexandra Savell, Teddy Huang, Nicoletta Cieri, ..., Robert J. Soiffer, X. Shirley Liu, Matthew S. Davids, Pavan Bachireddy, Catherine J. Wu

Blood   ·   16 Mar 2021   ·   doi:10.1182/blood.2021010867

Dissection of exceptional responses to CTLA-4 blockade in relapsed leukemia cutis after allogeneic stem cell transplantation.

leukemia cutis CTLA-4 blockade stem cell transplantation

2020

Personal tumor antigens in blood malignancies: genomics-directed identification and targeting

Livius Penter, Catherine J. Wu

Journal of Clinical Investigation   ·   27 Jan 2020   ·   doi:10.1172/JCI129209

Review of targets for cellular immunotherapies in blood malignancies.

mHAgs neoantigens stem cell transplantation immunogenomics

2019

Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)

Andrea Cossarizza, Hyun‐Dong Chang, Andreas Radbruch, Andreas Acs, Dieter Adam, ..., Yi Zhao, Susanne Maria Ziegler, Christina Zielinski, Jakob Zimmermann, Arturo Zychlinsky

European Journal of Immunology   ·   01 Oct 2019   ·   doi:10.1002/eji.201970107

Best practices for flow cytometry.

Localization-associated immune phenotypes of clonally expanded tumor-infiltrating T cells and distribution of their target antigens in rectal cancer

Livius Penter, Kerstin Dietze, Julia Ritter, Maria Fernanda Lammoglia Cobo, Josefin Garmshausen, ..., Sandra Wienzek-Lischka, Thomas Blankenstein, Michael Hummel, Klaus Dornmair, Leo Hansmann

OncoImmunology   ·   24 Mar 2019   ·   doi:10.1080/2162402X.2019.1586409

Phenotypes and T cell receptor sequences of tumor-infiltrating lymphocytes compared to physiologic tissue-resident T cells.

rectal cancer tumor-infiltrating lymphocytes PD-1

2018

FACS single cell index sorting is highly reliable and determines immune phenotypes of clonally expanded T cells

Livius Penter, Kerstin Dietze, Lars Bullinger, Jörg Westermann, Hans‐Peter Rahn, Leo Hansmann

European Journal of Immunology   ·   03 Apr 2018   ·   doi:10.1002/eji.201847507

Demonstration of the high accuracy of FACS index sorting using single T and B cell receptor sequencing.

FACS index sorting TCR BCR

2017

Clonal Expansion and Interrelatedness of Distinct B-Lineage Compartments in Multiple Myeloma Bone Marrow

Leo Hansmann, Arnold Han, Livius Penter, Michaela Liedtke, Mark M. Davis

Cancer Immunology Research   ·   31 Aug 2017   ·   doi:10.1158/2326-6066.cir-17-0012

Identification of myeloma clones in phenotypically healthy B cell compartment using B cell receptor sequencing.

2015

Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: a multicenter survey

R Zeiser, A Burchert, C Lengerke, M Verbeek, K Maas-Bauer, ..., C Peschel, A Neubauer, J Finke, J Duyster, N von Bubnoff

Leukemia   ·   31 Jul 2015   ·   doi:10.1038/leu.2015.212

A rapid screening system evaluates novel inhibitors of DNA methylation and suggests F-box proteins as potential therapeutic targets for high-risk neuroblastoma

Livius Penter, Bert Maier, Ute Frede, Benjamin Hackner, Thomas Carell, Christian Hagemeier, Matthias Truss

Targeted Oncology   ·   06 Jan 2015   ·   doi:10.1007/s11523-014-0354-5