Enriched Adaptive Immunity and Reduced Inflammatory Response in Plasma Cell Disorders of Self-Identified Black Patients
The immune tumor microenvironment (iTME) plays a crucial role in disease biology of plasma cell (PC) dyscrasias, but remains poorly characterized in self-identified Black individuals, a population at increased risk. Mass cytometry and scRNA-seq of 128 bone marrow aspirates revealed significant changes in immune cell composition across the disease spectrum, including shifts from naïve to effector T cells with declines in B cells, MAIT, pDCs, and increases in monocytes with disease progression. Self-identified Black patients had higher relative proportions of terminally differentiated T cells and lower monocytes in newly diagnosed and treated multiple myeloma (MM). ScRNA-seq revealed genes overexpressed in self-identified Black individuals were enriched for E2F targets and G2-M checkpoints, while reduced genes were enriched for TNF-α/NF-kB, interferon and inflammatory responses pathways. These findings were supported by genetic ancestry and validated in an independent dataset of 286 patients with MM from the MMRF Immune Atlas. Self-identified race and African genetic similarity are significantly associated with remodeling the MM iTME, with potential implications for disease biology and treatment response.
Authors
- Sivasankar Annamalai (ORCID: https://orcid.org/0000-0003-1282-9791)
- Abiola Bukunmi Bolarinwa (ORCID: https://orcid.org/0000-0001-5812-1954)
- William Pilcher (ORCID: https://orcid.org/0000-0002-8544-4967)
- Shaji Kunnathu Kumar (ORCID: https://orcid.org/0000-0001-5392-9284)
- Linda Banovic Baughn (ORCID: https://orcid.org/0000-0001-5229-4897)
- Suganti Shivaram
- Nadine H. Abdallah (ORCID: https://orcid.org/0000-0001-9195-1589)
- Mariam Khanfar (ORCID: https://orcid.org/0000-0002-3650-2665)
- Felicia Gomez (ORCID: https://orcid.org/0000-0003-4884-7510)
- Neeraj Sharma (ORCID: https://orcid.org/0000-0002-8229-3083)
- Cinthya J. Zepeda‐Mendoza (ORCID: https://orcid.org/0000-0002-0434-4965)
- Megan Moore Weivoda (ORCID: https://orcid.org/0000-0003-0240-0123)
- Joselle Cook (ORCID: https://orcid.org/0000-0001-5335-9533)
- S. Vincent Rajkumar (ORCID: https://orcid.org/0000-0002-5862-1833)
- Taxiarchis Kourelis (ORCID: https://orcid.org/0000-0001-8573-9434)
- Jinzhuang Dou (ORCID: https://orcid.org/0000-0003-0090-4264)
- Shulan Tian (ORCID: https://orcid.org/0000-0002-3348-7439)
- Surendra Dasari (ORCID: https://orcid.org/0000-0002-7972-3556)
- Emilie I. Anderson
- Hongwei Tang
- Manoj Bhasin
- Stacey J Lehman
- Mahek Bai
- Huihuang Yan
Institutions
- Georgia Institute of Technology (US)
- Mayo Clinic (US)
- Emory University (US)
- Washington University in St. Louis (US)
- University of Alabama at Birmingham (US)
- New York University (US)
Publication Details
- Journal
- Blood
- Published
- 2026-10-05
- DOI
- https://doi.org/10.1182/blood.2026033998
- Primary Topic
- Multiple Myeloma Research and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00