Abstract PR006: C5ORF30/MACIR is a regulator of HLA-DR expression and immune evasion in high-risk DLBCL

作者：Anand Devaprasath. Jeyasekharan, Z Ong, Michał Marek. Hoppe, Shruti Sridhar, Min Xian Wong, Irene Biju, Hong Liang, Mai P. Hoang, Patrick William. Jaynes, Yanfen Peng, Chartsiam Tipgomut, Sanjay De Mel, Limei Poon, Sheng‐Tsung Chang, Shih‐Sung Chuang, Siok-Bian Ng, Claudio Tripodo · 发表于：Blood Cancer Discovery · 年份：2026 · DOI：10.1158/2643-3249.lymphoma26-pr006 · 研究领域：Cancer Immunotherapy and Biomarkers、Ferroptosis and cancer prognosis、Phagocytosis and Immune Regulation

Abstract Understanding the molecular mechanisms governing relapse of diffuse large B-cell lymphoma (DLBCL) after R-CHOP immunochemotherapy is central to the development of novel therapeutic strategies. A recursive Bayesian screen across 13 gene expression datasets (N=3,775 patients) identified C5ORF30 (MACIR) as a strong and consistent predictor of poor survival, significant in 11 of 13 independent cohorts. MACIR is a relatively unknown cytoplasmic protein, described previously only in rheumatoid arthritis. We therefore evaluated its role and significance in DLBCL. We knockout-validated a MACIR antibody for immunohistochemistry (IHC) and evaluated its expression in reactive lymphoid tissues and DLBCL (N=250; 2 cohorts). In normal lymphoid tissues, MACIR protein was restricted to CD38-positive, CD20-negative plasmablast-like cells, pointing to a role in plasmacytic differentiation. In DLBCL, MACIR expression was noted in CD20-positive malignant B cells, especially in cases of ABC cell-of-origin. Importantly, MACIR protein expression remained independently prognostic of IPI and cell-of-origin on multivariate analysis. MACIR perturbation had minimal effects on proliferation, apoptosis, or sensitivity to CHOP chemotherapy in vitro, suggesting a non-cell-intrinsic role. In an immunocompetent syngeneic mouse model, Macir overexpression led to reduced T-cell infiltration, demonstrating a cell-extrinsic effect on the tumor immune microenvironment (TIME). We therefore examined MACIR’s...