Single-cell landscape analysis unravels molecular programming of the human B cell compartment in chronic GVHD

Poe, Jonathan C.; Fang, Jiyuan; Zhang, Dadong; Lee, Marissa; DiCioccio, Rachel A.; Su, Hsuan; Qin, Xiaodi; Zhang, Jennifer; Visentin, Jonathan; Bracken, Sonali; Ho, Vincent T.; Wang, Kathy S.; Rose, Jeremy J.; Pavletić, Steven Z.; Hakim, Frances T.; Jia, Wei; Suthers, Amy N.; Curry-Chisolm, Itaevia M.; Horwitz, Mitchell E.; Rizzieri, David A.; McManigle, William; Chao, Nelson J.; Cardones, Adela R.; Xie, Jichun; Owzar, Kouros; Sarantopoulos, Stefanie

doi:10.1172/jci.insight.169732

Cited by 6 publications

(2 citation statements)

References 95 publications

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“…Besides providing a deeper understanding of T cells, scRNA-seq studies of tissue biopsies should also investigate the role of other cell types in the pathogenesis of GvHD, such as B cells, for which Poe et al have provided a baseline by defining their transcriptional profiles in peripheral blood and bone marrow. 72 The possibilities of spatial transcriptomics in combination with the detection of immune cell receptor sequences 73,74 will enable the mapping of alloreactive cells to their cellular targets, and further refine our understanding of GvHD.…”

Section: Graft-versus-host Diseasementioning

confidence: 99%

Single-cell genomics-based immune and disease monitoring in blood malignancies

Rathgeber,

Ludwig,

Penter

2024

Clinical Hematology International

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Achieving long-term disease control using therapeutic immunomodulation is a long-standing concept with a strong tradition in blood malignancies. Besides allogeneic hematopoietic stem cell transplantation that continues to provide potentially curative treatment for otherwise challenging diagnoses, recent years have seen impressive progress in immunotherapies for leukemias and lymphomas with immune checkpoint blockade, bispecific monoclonal antibodies, and CAR T cell therapies. Despite their success, non-response, relapse, and immune toxicities remain frequent, thus prioritizing the elucidation of the underlying mechanisms and identifying predictive biomarkers. The increasing availability of single-cell genomic tools now provides a system’s immunology view to resolve the molecular and cellular mechanisms of immunotherapies at unprecedented resolution. Here, we review recent studies that leverage these technological advancements for tracking immune responses, the emergence of immune resistance, and toxicities. As single-cell immune monitoring tools evolve and become more accessible, we expect their wide adoption for routine clinical applications to catalyze more precise therapeutic steering of personal immune responses.

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Section: Graft-versus-host Diseasementioning

confidence: 99%

Single-cell genomics-based immune and disease monitoring in blood malignancies

Rathgeber,

Ludwig,

Penter

2024

Clinical Hematology International

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“…A recent single cell study reported the expansion of CD27 + memory and CD11c + atypical memory B cells in cGVHD patients, which can exhibit an exhausted phenotype. Trajectory analysis predicted that the cGVHD-expanded cluster develops along different trajectories compared to corresponding healthy control populations, bypassing tolerance checkpoints ( 76 ).…”

Section: Communication Of Immune Cells In Cgvhd – the Role Of B Cellsmentioning

confidence: 99%

Complex interactions of cellular players in chronic Graft-versus-Host Disease

et al. 2023

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Chronic Graft-versus-Host Disease is a life-threatening inflammatory condition that affects many patients after allogeneic hematopoietic stem cell transplantation. Although we have made substantial progress in understanding disease pathogenesis and the role of specific immune cell subsets, treatment options are still limited. To date, we lack a global understanding of the interplay between the different cellular players involved, in the affected tissues and at different stages of disease development and progression. In this review we summarize our current knowledge on pathogenic and protective mechanisms elicited by the major involved immune subsets, being T cells, B cells, NK cells and antigen presenting cells, as well as the microbiome, with a special focus on intercellular communication of these cell types via extracellular vesicles as up-and-coming fields in chronic Graft-versus-Host Disease research. Lastly, we discuss the importance of understanding systemic and local aberrant cell communication during disease for defining better biomarkers and therapeutic targets, eventually enabling the design of personalized treatment schemes.

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