Characterization of Immune Cell Subsets of Tumor Infiltrating Lymphocytes in Brain Metastases

Autor: Priyakshi Kalita-de Croft, Haarika Chittoory, Tam H. Nguyen, Jodi M. Saunus, Woo Gyeong Kim, Amy E. McCart Reed, Malcolm Lim, Xavier M. De Luca, Kaltin Ferguson, Colleen Niland, Roberta Mazzieri, Riccardo Dolcetti, Peter T. Simpson, Sunil R. Lakhani
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Biology, Vol 10, Iss 5, p 425 (2021)
Druh dokumentu: article
ISSN: 2079-7737
DOI: 10.3390/biology10050425
Popis: The heterogeneity of tumor infiltrating lymphocytes (TILs) is not well characterized in brain metastasis. To address this, we performed a targeted analysis of immune-cell subsets in brain metastasis tissues to test immunosuppressive routes involved in brain metastasis. We performed multiplex immunofluorescence (mIF), using commercially available validated antibodies on formalin-fixed paraffin embedded whole sections. We quantitated the subsets of immune-cells utilizing a targeted panel of proteins including PanCK, CD8, CD4, VISTA and IBA-1, and analyzed an average of 15,000 cells per sample. Classifying tumors as either high (>30%) or low (p < 0.01) as well as in their microenvironment (p < 0.001). Contrastingly, the tumors with high TILs displayed higher levels of microglia, as measured by IBA-1 expression. Low TILs-tumors displayed CD8+ T-cells that co-express VISTA (p < 0.01) significantly more compared to high TILs group, where CD8+cells significantly co-express IBA-11 (p < 0.05). These results were supported by RNA analysis of a publicly available, independent cohort. Our work contributes to a growing understanding of the immune surveillance escape routes active in brain metastasis.
Databáze: Directory of Open Access Journals