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.
Jithendra Kini Bailur, Samuel S. McCachren, Deon B. Doxie, Mahesh Shrestha, Katherine Pendleton, Ajay K. Nooka, Natalia Neparidze, Terri L. Parker, Noffar Bar, Jonathan L. Kaufman, Craig C. Hofmeister, Lawrence H. Boise, Sagar Lonial, Melissa L. Kemp, Kavita M. Dhodapkar, Madhav V. Dhodapkar
This file is in Adobe Acrobat (PDF) format. If you have not installed and configured the Adobe Acrobat Reader on your system.
PDFs are designed to be printed out and read, but if you prefer to read them online, you may find it easier if you increase the view size to 125%.
Many versions of the free Acrobat Reader do not allow Save. You must instead save the PDF from the JCI Online page you downloaded it from. PC users: Right-click on the Download link and choose the option that says something like "Save Link As...". Mac users should hold the mouse button down on the link to get these same options.