bims-migras 2026-01-18 papers

Issue of 2026–01–18
four papers selected by
Cliff Dominy

Hum Mutat. 2026 ;2026 8778797

Integrated Multiomics Analysis Reveals a Migrasome-Related Signature for Prognosis and Immunotherapy Response in Lung Adenocarcinoma.

Jiayu Zhou, Tianye Song, Nengzheng Wang, Ce Liang, Ming Jiang, Xu Zhang, Hong Gao, Qingqing Feng, Sujit Nair.

Background: Migrasomes, a newly identified subtype of extracellular vesicles generated during cell migration, play crucial roles in tumor microenvironment modulation. However, their systematic characterization in lung adenocarcinoma (LUAD) remains unexplored. This study is aimed at deciphering migrasome-related molecular features and their clinical significance through multiomics integration.
Methods: We integrated bulk transcriptomes (541 LUAD samples from TCGA/GEO) with single-cell RNA-seq (GSE156632). Migrasome-related genes (MIGgenes) were identified through WGCNA and differential expression analysis. A machine learning framework incorporating 10 algorithms generated 101 combinatorial models, with the optimal prognostic signature (MIGsig) selected via 10-fold cross-validation. Biological mechanisms were investigated through ssGSEA, TME analysis, and in vitro validation.
Results: Our analysis revealed significant migrasome activity enrichment in endothelial cells and fibroblasts, with 115 cross-omics MIGgenes identified including 31 prognostic markers. The Lasso-Cox-derived 3-gene signature (GSTM5/DNASE1L3/PDGFB) demonstrated robust predictive performance (training set C index = 0.703; validation set GSE50081 AUC = 0.678). The low-MIGsig group exhibited characteristic "hot tumor" features, including elevated immune infiltration and higher tumor mutational burden, and significantly improved immunotherapy response rates in the IMvigor210 cohort. Finally, MIGsig-related genes were further validated by in vitro experiments and public database.
Conclusions: This study establishes the first migrasome-based prognostic model for LUAD, demonstrating both independent survival prediction capability and clinical utility for identifying immunotherapy beneficiaries. The MIGsig signature provides novel biological insights into migrasome-mediated tumor-immune interactions and represents a promising tool for precision oncology applications in LUAD management.

Keywords: immunotherapy prediction; lung adenocarcinoma; machine learning; migrasomes; tumor microenvironment

DOI: https://doi.org/10.1155/humu/8778797

Mol Oncol. 2026 Jan 12.

Cell surface interactome analysis identifies TSPAN4 as a negative regulator of PD-L1 in melanoma.

Guus A Franken, Andrea Abel Gutierrez, Imke van Rossum, Cornelia G Spruijt, Michiel Vermeulen, Guido van Mierlo, Blanca Scheijen, Annemiek B van Spriel.

PD-L1 is a key immune checkpoint ligand that suppresses antitumor immunity by engaging PD-1 on T cells. While therapeutic blockade of PD-L1/PD-1 interactions has shown clinical benefit, many patients fail to respond, indicating modulation by other factors. Here, we identified a novel regulatory axis in which the membrane-organizing protein tetraspanin-4 (TSPAN4) modulates PD-L1 in melanoma cells. Using cell surface proximity biotinylation coupled with mass spectrometry, we discovered that TSPAN4 physically associates with PD-L1, with both proteins colocalizing on migrasomes and retraction fibers. Mechanistically, we show that TSPAN4 negatively regulates PD-L1 protein levels by enhancing its degradation and restricting its lateral mobility at the plasma membrane. Loss of TSPAN4 stabilized PD-L1, promoted its interaction with CMTM6, and increased PD-L1 surface availability for PD-1 binding. Functionally, TSPAN4 knockdown in melanoma cells led to more efficient immune checkpoint blockade through PD-1 on T cells. This study identifies TSPAN4 as a negative regulator of PD-L1 at the cell surface of melanoma cells suggesting that targeting TSPAN4 may offer a new therapeutic strategy to enhance immune checkpoint blockade in melanoma and other cancers.

Keywords: PD‐L1; TSPAN4; cell surface proximity biotinylation; melanoma

DOI: https://doi.org/10.1002/1878-0261.70182

Biomark Res. 2026 Jan 16.

Migrasome and cancer - from cellular to clinical perspectives.

Zijie Guo, Yihong Wen, Qina He, Ziyu Zhu, Xixi Lin, Maryam Maleki Goli, Parnia Ghanad, Feiyang Ji, Linbo Wang, Lili Zhi, Jichun Zhou.

Keywords: Cancer; Cancer biology; Cell migration; Clinical application; Migrasome; Tumor microenvironment

DOI: https://doi.org/10.1186/s40364-026-00893-4