Early alterations in stem-like/marrow-resident T cells and innate and myeloid cells in preneoplastic gammopathy

Jithendra Kini, Bailur, Emory University; Samuel S., McCachren, Emory University; Deon B., Doxie, Emory University; Mahesh, Shrestha, Emory University; Katherine, Pendleton, Emory University; Ajay, Nooka, Emory University; Natalia, Neparidze, Yale University; Terri L., Parker, Yale University; Noffar, Bar, Yale University; Jonathan, Kaufman, Emory University; Craig, Hofmeister, Emory University; Lawrence, Boise, Emory University; Sagar, Lonial, Emory University; Melissa, Kemp, Emory University; Kavita, Dhodapkar, Emory University; Madhav, Dhodapkar, Emory University

Persistent URL

https://open.library.emory.edu/purl/511xd254tm-emory

Last modified

05/22/2025

Type of Material

Article

Authors

Jithendra Kini Bailur, Emory University

Samuel S. McCachren, Emory University

Deon B. Doxie, Emory University

Mahesh Shrestha, Emory University

Katherine Pendleton, Emory University

Ajay Nooka, Emory UniversityNatalia Neparidze, Yale UniversityTerri L. Parker, Yale UniversityNoffar Bar, Yale UniversityJonathan Kaufman, Emory UniversityCraig Hofmeister, Emory UniversityLawrence Boise, Emory UniversitySagar Lonial, Emory UniversityMelissa Kemp, Emory UniversityKavita Dhodapkar, Emory UniversityMadhav Dhodapkar, Emory University

Language

English

Date

2019-06-06

Publisher

AMER SOC CLINICAL INVESTIGATION INC

Publication Version

Final Published Version

Copyright Statement

© 2019, American Society for Clinical Investigation.

Final Published Version (URL)

http://dx.doi.org/10.1172/jci.insight.127807

Title of Journal or Parent Work

JCI insight

ISSN

2379-3708

Volume

4

Issue

11

Grant/Funding Information

MVD is supported in part by funds from the NIH (R35CA197603), Leukemia and Lymphoma Society Translational Research Program, International Waldenstrom Macroglobulinemia Foundation, and a Multiple Myeloma Research Foundation-Perelman Family Foundation Early Disease Translational Research grant.

Supplemental Material (URL)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6629164/bin/jciinsight-4-127807-s136.pdf

Abstract

Preneoplastic lesions carry many of the antigenic targets found in cancer cells but often exhibit prolonged dormancy. Understanding how the host response to premalignancy is maintained and altered during malignant transformation is needed to prevent cancer. To understand the immune microenvironment in precursor monoclonal gammopathy of undetermined significance (MGUS) and myeloma, we analyzed bone marrow immune cells from 12 healthy donors and 26 patients with MGUS/myeloma by mass cytometry and concurrently profiled transcriptomes of 42,606 single immune cells from these bone marrow samples. Compared with age-matched healthy donors, memory T cells from both MGUS and myeloma patients exhibited greater terminal effector differentiation. However, memory T cells in MGUS show greater enrichment of stem-like TCF1/7hi cells. Clusters of T cells with stem-like and tissue residence genes were also found to be enriched in MGUS by single-cell transcriptome analysis. Early changes in both NK and myeloid cells were also observed in MGUS. Enrichment of stem-like T cells correlated with a distinct genomic profile of myeloid cells and levels of Dickkopf-1 in bone marrow plasma. These data describe the landscape of changes in both innate and adaptive immunity in premalignancy and suggest that attrition of the bone marrow–resident T cell compartment because of loss of stem-like cells may underlie loss of immune surveillance in myeloma.

Author Notes