What type of study is this?

This is a Pre-Registered Trial study.

What question did this study set out to answer?

To define the pathogenic mechanisms of immune effector cell-associated hemophagocytic-like syndrome (IEC-HS) following CD22 CAR T-cell therapy.

December 8, 2025BloodOpen Access

A novel immune signature characterized by activation of the IFNγ-IL18 axis identifies immune effector cell-associated HLH-like syndrome after CD22 chimeric antigen receptor T-cell therapy

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Authors

JRJoseph M. RoccoNational Institutes of Health LCL CookHealth Canada TLThomas LangowskiNational Institutes of Health

Discussion

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Implication

Analysis reveals activation of inflammasome and T-cell pathways in immune effector cell-associated HLH post CAR T-cell therapy, indicating potential therapeutic targets.

Key Points

To define the pathogenic mechanisms of immune effector cell-associated hemophagocytic-like syndrome (IEC-HS) following CD22 CAR T-cell therapy.
Conducted plasma proteomic evaluation using SomaScan® in patients with IEC-HS vs controls.
Performed single cell RNA sequencing on peripheral blood at IEC-HS onset.
Executed spatial transcriptomics on bone marrow biopsy samples pre- and post-CAR T-cell therapy.
IEC-HS patients exhibited a distinct immune signature characterized by elevated inflammatory cytokines.
Significant activation of pathways related to cell proliferation and type II interferon signaling observed at IEC-HS onset.
Increased presence of myeloid progenitors and markers of innate immune activation detected in bone marrow.

Cite This Study

Rocco et al. (2025) studied this question.

synapsesocial.com/papers/69362f764fa91c937236e3f8 https://doi.org/10.1182/blood-2025-2344

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Implication

Analysis reveals activation of inflammasome and T-cell pathways in immune effector cell-associated HLH post CAR T-cell therapy, indicating potential therapeutic targets.

A novel immune signature characterized by activation of the IFNγ-IL18 axis identifies immune effector cell-associated HLH-like syndrome after CD22 chimeric antigen receptor T-cell therapy

Discussion

Member takes

Implication

Key Points

Cite This Study

A novel immune signature characterized by activation of the IFNγ-IL18 axis identifies immune effector cell-associated HLH-like syndrome after CD22 chimeric antigen receptor T-cell therapy

Discussion

Member takes

Implication

Key Points

Cite This Study

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