Response to azacitidine and the TIM-3 inhibitor, sabatolimab, in MDS and CMML is associated with distinct immune and antigen-presentation states

In MDS treated with azacitidine plus sabatolimab, baseline HLA class II-high antigen-presentation states and CD8/NK interferon programs are linked to response, with nonresponders bypassing HLA class II-high differentiation.

• Why it matters: TIM-3 blockade is promising in myeloid neoplasms, but the hematopoietic and immune states that predict or accompany anti-TIM-3 benefit are not well defined.
• What they did: Single-cell RNA sequencing and CITE-seq profiled bone marrow and peripheral blood from MDS and CMML patients on azacitidine plus sabatolimab, compared with Human Cell Atlas references, and used trajectory and immune-state analyses.
• The result: Responders in MDS and CMML showed coordinated remodeling, including contraction of BM CD8 and CD4 T cells with type I interferon and inflammatory programs (IFIT1, IFIT2, TNF) and expansion of a GZMH/IFITM1-expressing cytotoxic CD8 T-cell population.

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