Multi-modal analysis reveals tumor and immune features distinguishing EBV-positive and EBV-negative post-transplant lymphoproliferative disorders
The oncogenic Epstein-Barr virus (EBV) can drive tumorigenesis with disrupted host immunity, causing malignancies including post-transplant lymphoproliferative disorders (PTLDs). PTLD can also arise in the absence of EBV, but the biological differences underlying EBV(+) and EBV(-) B cell PTLD and the associated host-EBV-tumor interactions remain poorly understood. Here, we reveal the core differences between EBV(+) and EBV(-) PTLD, characterized by increased expression of genes related to immune processes or DNA interactions, respectively, and the augmented ability of EBV(+) PTLD B cells to modulate the tumor microenvironment through elaboration of monocyte-attracting cytokines/chemokines. We create a reference resource of proteins distinguishing EBV(+) B lymphoma cells from EBV(-) B lymphoma including the immunomodulatory molecules CD300a and CD24, respectively. Moreover, we show that CD300a is essential for maximal survival of EBV(+) PTLD B lymphoma cells. Our comprehensive multi-modal analyses uncover the biological underpinnings of PTLD and offer opportunities for precision therapies.
Authors
- Yasodha Natkunam (ORCID: https://orcid.org/0000-0002-9816-1018)
- Francesco Vallania (ORCID: https://orcid.org/0000-0003-0098-249X)
- Govind Bhagat (ORCID: https://orcid.org/0000-0001-6250-048X)
- Steven H. Swerdlow (ORCID: https://orcid.org/0000-0002-3832-3329)
- Andrea Reitsma (ORCID: https://orcid.org/0009-0005-9840-5376)
- Daan Dierickx (ORCID: https://orcid.org/0000-0002-8917-022X)
- Olivia M. Martinez (ORCID: https://orcid.org/0000-0002-2798-0251)
- Sheri M. Krams (ORCID: https://orcid.org/0000-0002-6049-5119)
- Ananthakrishnan Ganesan (ORCID: https://orcid.org/0000-0001-6242-4261)
- James T. Harden
- Marla C. Glass (ORCID: https://orcid.org/0000-0003-3763-0842)
- Fiona E. Craig (ORCID: https://orcid.org/0000-0003-1743-3454)
- Julie Morscio (ORCID: https://orcid.org/0000-0002-0102-4667)
- Ansuman T. Satpathy (ORCID: https://orcid.org/0000-0002-5167-537X)
- Jiaying Toh (ORCID: https://orcid.org/0000-0003-2939-9206)
- E. Y. LEE
- Laurynas Kalesinskas (ORCID: https://orcid.org/0000-0002-2903-2378)
- Sheren F. Younes
- Tetsuya Tajima (ORCID: https://orcid.org/0000-0002-6538-7408)
- Purvesh Khatri (ORCID: https://orcid.org/0000-0002-4143-4708)
- Thomas Tousseyn (ORCID: https://orcid.org/0000-0002-0397-1086)
- Edward A. Vizcarra (ORCID: https://orcid.org/0000-0002-7591-550X)
- Xi Wang (ORCID: https://orcid.org/0000-0003-3566-4192)
- Shuchun Zhao (ORCID: https://orcid.org/0000-0002-0562-6817)
- Josselyn K. Peña
- K. Jenkins
- Joy A. Pai (ORCID: https://orcid.org/0009-0000-3529-6671)
- Irene Liang
- Chimere Ezeiruaku
Institutions
- University of Pittsburgh (US)
- California Institute for Regenerative Medicine (US)
- Institute for Stem Cell Biology and Regenerative Medicine (IN)
- Mayo Clinic in Arizona (US)
- Mayo Clinic Hospital (US)
- Stanford Medicine (US)
- Columbia University (US)
- Stanford University (US)
- KU Leuven (BE)
Publication Details
- Journal
- Cell Reports Medicine
- Published
- 2024-12-01
- DOI
- https://doi.org/10.1016/j.xcrm.2024.101851
- Citations
- 8
- Primary Topic
- Viral-associated cancers and disorders
- Type
- article
- Field-Weighted Citation Impact
- 2.26
Funders
- U.S. Department of Defense
- Bill and Melinda Gates Foundation
- Stanford University
- Agency for Science, Technology and Research
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases