PT  - JOURNAL ARTICLE
AU  - Xiaojun Ma
AU  - David Lembersky
AU  - Elena S Kim
AU  - Tullia C Bruno
AU  - Joseph R. Testa
AU  - Hatice U Osmanbeyoglu
TI  - Spatial landscape of malignant pleural and peritoneal mesothelioma tumor immune microenvironment
AID  - 10.1101/2023.09.06.556559
DP  - 2023 Jan 01
TA  - bioRxiv
PG  - 2023.09.06.556559
4099  - http://biorxiv.org/content/early/2023/09/07/2023.09.06.556559.short
4100  - http://biorxiv.org/content/early/2023/09/07/2023.09.06.556559.full
AB  - Immunotherapies have shown modest clinical benefit thus far for malignant mesothelioma (MM). A deeper understanding of immune cell spatial distribution within the tumor immune microenvironment (TIME) is needed to identify interactions between tumor and different immune cell types that might impact the effectiveness of potential immunotherapies. We performed multiplex immunofluorescence (mIF) using tissue microarrays (TMAs, n=3) of samples from patients with malignant peritoneal (n=25) and pleural (n=88) mesothelioma (MPeM and MPM, respectively) to elucidate the spatial distributions of major immune cell populations and their association with LAG3, BAP1, NF2, and MTAP expression, the latter as a proxy for CDKN2A/B. We also analyzed the relationship between the spatial distribution of major immune cell types with MM patient prognosis and clinical features. The distribution of immune cells within the TIME is similar between MPM and MPeM. However, there is a higher level of interaction between immune cells and tumor cells in MPM than MPeM. Within MPM tumors, there is increased amount of interaction between tumor cells and CD8+ T cells in BAP1-low than in BAP1-high expressing tumors. The cell-cell interactions identified in this investigation have potential implications for the immune response against MM tumors and could be a factor in the different behaviors of MPM and MPeM. Our findings provide a valuable resource for the MM cancer research community and exemplifies the utility of spatial resolution within single-cell analyses.Our mesothelioma spatial atlas mIF dataset is available at https://mesotheliomaspatialatlas.streamlit.app/.Competing Interest StatementJRT has provided legal consultation regarding the role of genetic alterations in MM. The remaining authors declare no conflict of interest.