**Author Listing - Lead/ Submitting Author (we will be communicating with this individual): Name, Institution, City and State where the work was done. Co-authors will be added in a separate section.**
Theophilus Tandoh
Judy and Bernard Briskin Center for Multiple Myeloma Research; Department of Hematologic Malignancies Translational Science, Beckman Research Institute; City of Hope.
Duarte, CA

**Main Body of the Abstract**
Background: Light chain amyloidosis (AL) is a disease marked by abnormal plasma cells (PCs) constitutively producing structurally aberrant monoclonal free light chains, which deposit in multiple organs including bone marrow (BM). Although AL shares several genetic characteristics and therapeutic treatments with multiple myeloma (MM), the possible effect of amyloidogenic monoclonal plasma cells and amyloid fibrils on the BM immune environment has not been fully characterized. Using single-cell mass cytometry analysis (CyTOF), the present study aimed to investigate the characteristics of immune cells and malignant PCs in the BM of newly diagnosed patients with untreated AL (n=8) compared with the characteristics in healthy donors (HD, n=5) and patients with untreated high-risk smoldering and newly diagnosed MM (n=6).
Results: Supervised machine learning algorithm (CITRUS) and FlowSOM analyses showed that, when compared with HDs, the AL-BM showed significant upregulation of the antigen-specific suppressive TIGIT+CD8+ NKT-like cells (p=0.014) (Fig.1A), an increase in exhausted PD-1+ (p=0.047) and TIGIT+ CD8+ T cells (p=0.002), and down-regulation of promonocytes (p=0.04). Conversely, no significant differences were found between MM and HD. Compared to MM, the AL-BM is significantly enriched in CD4+ central memory T cells (p=0.035) (Fig.1B), but no differences were observed in specific PCs makers, including BCMA, CD38, CS1, and CD56.
Conclusion: Our preliminary data show that the BM of AL patients, but not MM patients, display a more prominent immune suppressive signature compared to HD. Understanding specific AL immune disruptions can offer insights into the disease and the potential for developing AL-directed strategies.



**Author Listing - Lead/ Submitting Author (we will be communicating with this individual): Name, Institution, City and State where the work was done. Co-authors will be added in a separate section.**
Theophilus Tandoh
Judy and Bernard Briskin Center for Multiple Myeloma Research; Department of Hematologic Malignancies Translational Science, Beckman Research Institute; City of Hope.
Duarte, CA

**Main Body of the Abstract**
**Background:** Light chain amyloidosis (AL) is a disease marked by abnormal plasma cells (PCs) constitutively producing structurally aberrant monoclonal free light chains, which deposit in multiple organs including bone marrow (BM). Although AL shares several genetic characteristics and therapeutic treatments with multiple myeloma (MM), the possible effect of amyloidogenic monoclonal plasma cells and amyloid fibrils on the BM immune environment has not been fully characterized. Using single-cell mass cytometry analysis (CyTOF), the present study aimed to investigate the characteristics of immune cells and malignant PCs in the BM of newly diagnosed patients with untreated AL (n=8) compared with the characteristics in healthy donors (HD, n=5) and patients with untreated high-risk smoldering and newly diagnosed MM (n=6).
**Results:** Supervised machine learning algorithm (CITRUS) and FlowSOM analyses showed that, when compared with HDs, the AL-BM showed significant upregulation of the antigen-specific suppressive TIGIT+CD8+ NKT-like cells (p=0.014) (**Fig.1A**), an increase in exhausted PD-1+ (p=0.047) and TIGIT+ CD8+ T cells (p=0.002), and down-regulation of promonocytes (p=0.04). Conversely, no significant differences were found between MM and HD. Compared to MM, the AL-BM is significantly enriched in CD4+ central memory T cells (p=0.035) (**Fig.1B**), but no differences were observed in specific PCs makers, including BCMA, CD38, CS1, and CD56.
**Conclusion:** Our preliminary data show that the BM of AL patients, but not MM patients, display a more prominent immune suppressive signature compared to HD. Understanding specific AL immune disruptions can offer insights into the disease and the potential for developing AL-directed strategies.



Single-Cell Mass Cytometry Analysis Reveals a Prominent Immune Suppressive Signature in AL Amyloidosis PA48 (#525)

We invite you to attend the XIX International Symposium on Amyloidosis to be held in Rochester, MN.

This symposium is organized as a hybrid meeting (with the focus on in-person) held from Sunday, May 26 through Thursday, May 30, 2024.

Together with the ISA Board and members of Mayo Clinic, a very attractive scientific hybrid program is being planned. The program will cover a variety of types of systemic amyloidosis: ATTR (hereditary and wild-type), AL (light-chain), AA and less frequent forms. There will be key lectures, specific symposia including those company sponsored, oral presentations and poster sessions of accepted abstracts.

COURSE DESCRIPTION
This program will provide a comprehensive review of state-of-the-art education in systemic amyloidosis: basic science, pathophysiology, diagnosis, current and emerging treatments. Scientific presentations will include competitive oral and poster abstracts. The rapid evolution of scientific discovery and expanding treatment options has created tremendous interest in the field and this meeting will fill and important gap in educating scientists and clinicians.