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bioRxiv · 10.64898/2026.08.23.746487

C1Q-associated adaptive myeloid remodelling accompanies early response to BCMA CAR-T therapy in multiple myeloma

Wang, S.·Wang, Q.·Li, Y.-R.·Li, S.
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Abstract

BCMA-directed chimeric antigen receptor T cells induce deep responses in multiple myeloma, yet the immune ecology accompanying early response remains incompletely resolved. We reanalysed 171,971 single-cell transcriptomes from 25 peripheral-blood and bone-marrow specimens from ten patients. At day 30, responders showed concordant enrichment of C1Q and IFN-{gamma} programmes in blood and marrow myeloid pseudobulk profiles. Antigen-presentation genes were enriched in blood, whereas TGF-{beta} and hypoxia programmes were depleted in responding marrow. Cholesterol-efflux genes were not enriched in responders or after treatment. A composite C1Q-cholesterol score showed nominal associations with response and CD8 dysfunction in selected compartments, but none survived study-wide correction. The pathway results support an adaptive, antigen-presenting C1Q-associated programme rather than a uniformly suppressive C1Q macrophage model. This state-contingent interpretation of early myeloid remodelling requires prospective, patient-level validation before biomarker or causal claims are warranted.

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Wang, S., Wang, Q., Li, Y.-R., Li, S.. 2026-08-25. C1Q-associated adaptive myeloid remodelling accompanies early response to BCMA CAR-T therapy in multiple myeloma. https://doi.org/10.64898/2026.08.23.746487

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