Houliang Zhang

Southeast University, China

Title: SPP1+ Macrophage-Induced CD74+ Tumor Cells Promote Adrenocortical Carcinoma Tumor Thrombosis Via The SPP1/CD44/JAK/STAT Signaling

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Biography

Houliang Zhang is a Ph.D. candidate in Urology at Zhongda Hospital, Southeast University. His research focuses on the tumor microenvironment and metastatic mechanisms of urological cancers, particularly adrenocortical carcinoma and renal cell carcinoma. To date, he has published his findings as first author in high-impact journals, including Advanced Science and Advanced Functional Materials. His work integrates multiomics approaches, such as single-cell RNA sequencing and spatial transcriptomics, to identify novel therapeutic targets.

Abstract

Adrenocortical carcinoma (ACC) is a rare and aggressive endocrine malignancy with limited treatment options and poor prognosis, especially when complicated by venous tumor thrombus (VTT). Using integrated multiomics analysis of an ACC patient with VTT, we performed single- cell RNA sequencing (scRNA- seq), spatial transcriptomics (ST), and functional assays on primary tumor, VTT tail, and VTT head regions. scRNA- seq and ST revealed marked enrichment of CD74? tumor cells in the VTT head. Functional experiments showed that CD74 overexpression significantly enhanced the migration, invasion, and proliferation of ACC cell lines (SW- 13 and H295R) both in vitro and in vivo, and activated the JAK- STAT signaling pathway. Spatial and cellular interaction analyses further identified that SPP1? macrophages closely juxtaposed with CD74? tumor cells in the VTT head, and the SPP1- CD44 ligand- receptor axis mediated this crosstalk. Neutralizing CD44 abrogated CD74- induced malignant phenotypes, while SPP1 overexpression potentiated CD74- driven JAK2/STAT3 activation and ACC progression. Our findings uncover a novel mechanism by which SPP1? macrophages promote ACC tumor thrombosis through the SPP1/CD44/JAK/STAT axis targeting CD74? tumor cells. This study provides potential therapeutic targets and highlights CD74 as a promising candidate for future immunotherapy in ACC.