Exploration of the personalized immune checkpoint atlas of plasma cell dyscrasias patients using high‑dimensional single‑cell analysis

Abstract

Immune checkpoint blockade endows patients with unparalleled success in conquering cancer. Unfortunately, inter-individual heterogeneity causes failure in controlling tumors in many patients. Emerging mass cytometry technology is capable of revealing a multiscale onco-immune landscape that improves the efficacy of cancer immunotherapy. We introduced mass cytometry to determine the personalized immune checkpoint status in bone marrow and peripheral blood samples from 3 patients with multiple myeloma, amyloid light-chain amyloidosis, and solitary bone plasmacytoma and 1 non-hematologic malignancy patient. The expression of 18 immune regulatory receptors and ligands on 17 defined cell populations was simultaneously examined. By single-cell analyses, we identified the T cell clusters that serve as immunosuppressive signal source and revealed integrated immune checkpoint axes of individuals, thereby providing multiple potential immunotherapeutic targets, including programmed cell death protein 1 (PD-1), inducible co-stimulator (ICOS), and cluster of differentiation 28 (CD28), for each patient. Distinguishing the cell populations that function as providers and receivers of the immune checkpoint signals demonstrated a distinct cross-interaction network of immunomodulatory signals in individuals. These in-depth personalized data demonstrate mass cytometry as a powerful innovation to discover the systematical immune status in the primary and peripheral tumor microenvironment.

Immune checkpoint expression patterns on T cell subsets in light-chain amyloidosis: VISTA, PD-1, and TIGIT as potential therapeutic targets

“…In MM, BM represents an immunosuppressive microenvironment that can impair the function of T cells, 38 and we have identified increased exhausted T cells in BM of MM patients in our previous studies, 17 , 29 nevertheless T cell alterations within the BM microenvironment in AL are poorly understood. Thus we further evaluated the frequency of VISTA + , PD-1 + , Tim-3 + , and TIGIT + T-cell in BM samples, however, no differences were found between patients with AL amyloidosis and HIs.…”

T cell landscape and dynamics in immunoglobulin light chain amyloidosis before and after daratumumab‐based therapy

“… 12 The impact of these seemingly limited T cell alterations on disease progression is not known. 14 An elevation of CD8 + T and a reduction of CD4 + T cell frequencies in the BM were observed in MM patients treated with bortezomib, lenalidomide or autologous stem cell transplantation. 9 Whether these treatments lead to similar changes in patients with AL has not been directly examined.…”