Stromal localization of inactive CD8+ T cells in metastatic mismatch repair deficient colorectal cancer
Menée à partir de l'analyse de 46 727 cellules à l'aide d'une technique d'imagerie par cytométrie de masse et menée à partir de l'analyse de l'abondance et de la distribution spatiale des fibroblastes et des cellules immunitaires de tumeurs colorectales primitives, cette étude évalue l'association entre les caractéristiques des microenvironnements immunitaire et stromal des tumeurs présentant un haut niveau d'instabilité des microsatellites et le risque de développer des métastases
Background : The determinants of metastasis in mismatch repair deficiency with high levels of microsatellite instability (MSI-H) in colorectal cancer (CRC) are poorly understood. Here, we hypothesized that distinct immune and stromal microenvironments in primary tumors may discriminate between non-metastatic MSI-H CRC and metastatic MSI-H CRC.
Methods : We profiled 46,727 single cells using high-plex imaging mass cytometry and analyzed both differential cell type abundance, and spatial distribution of fibroblasts and immune cells in primary CRC tumors with or without metastatic capacity. We validated our findings in a second independent cohort using immunohistochemistry.
Results : High-plex imaging mass cytometry and hierarchical clustering based on microenvironmental markers separated primary MSI-H CRC tumors with and without metastatic capacity. Primary tumors with metastatic capacity displayed a high stromal content and low influx of CD8+ T cells, which expressed significantly lower levels of markers reflecting proliferation (Ki67) and antigen-experience (CD45RO) compared to CD8+ T cells in non-metastatic tumors. CD8+ T cells showed intra-epithelial localization in non-metastatic tumors, but stromal localization in metastatic tumors, which was validated in a second cohort.
Conclusion : We conclude that localization of phenotypically distinct CD8+ T cells within stroma may predict metastasis formation in MSI-H CRC.
British Journal of Cancer , résumé, 2023