2020
DOI: 10.1038/s41467-020-19408-2
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Integrated digital pathology and transcriptome analysis identifies molecular mediators of T-cell exclusion in ovarian cancer

Abstract: Close proximity between cytotoxic T lymphocytes and tumour cells is required for effective immunotherapy. However, what controls the spatial distribution of T cells in the tumour microenvironment is not well understood. Here we couple digital pathology and transcriptome analysis on a large ovarian tumour cohort and develop a machine learning approach to molecularly classify and characterize tumour-immune phenotypes. Our study identifies two important hallmarks characterizing T cell excluded tumours: 1) loss of… Show more

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Cited by 153 publications
(194 citation statements)
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References 62 publications
(64 reference statements)
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“…The myeloid cells also showed abundant and distinct PD-L1 expression profiles between the HR genotypes, with the highest expression in the CD11c+ cells in the BRCA1/2mut tumors and M2-type macrophages in the HRwt tumors. Overall, the infiltration of CD8+ and CD4+T-cells correlated positively with the infiltration of various macrophages, as suggested also previously 14 .…”
Section: Discussionsupporting
confidence: 88%
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“…The myeloid cells also showed abundant and distinct PD-L1 expression profiles between the HR genotypes, with the highest expression in the CD11c+ cells in the BRCA1/2mut tumors and M2-type macrophages in the HRwt tumors. Overall, the infiltration of CD8+ and CD4+T-cells correlated positively with the infiltration of various macrophages, as suggested also previously 14 .…”
Section: Discussionsupporting
confidence: 88%
“…By contrast, the epithelial cells with a higher proliferative state were residing outside of the CD4+ or CD8+T-cell neighborhoods in the HRwt tumors. Notably, the proportions of proliferating epithelial tumor cells correlated negatively with CD8+ and CD4+T-cell infiltration, as suggested also by a previous report 14 , indicating that the immune surveillance of CD8+ and CD4+T-cells towards the highly proliferating epithelial cells in the BRCA1/2mut tumors is regulated by spatial attraction and not just by cellular abundance. Our single-cell spatial TME analysis thus suggests that these tumor-immune spatial communities further contribute to the prognostic roles of T-cell infiltration and tumor cell proliferative states observed in the HR-genotypes.…”
Section: Discussionsupporting
confidence: 84%
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“…The examples summarized in Table 2 , as well as the example shown in Figure 3 from Desbois et al [ 153 ] show the immense power of the applications of this technique utilizing next-generation digital pathology for the assessment of the immune tumor microenvironment. In order to integrate the Immunoscore or other immune cell screening strategies also into clinical research, such fully automated next-generation digital pathology platforms should be implemented into the process of quantification of the rate of infiltration of various immune cell populations/markers.…”
Section: Current Applications Of Next-generation Digital Pathologymentioning
confidence: 99%