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De Palma, M.

Publications and source records attributed to De Palma, M..

4 recordsLinked to original sources

LuTuFlow: a deep learning-based pipeline for quantitative characterization of mouse lung tumors in CT imaging

Computed tomography (CT) is a widely used, non-invasive imaging tool to monitor tumor growth. Tumor identification and volumetric quantification are crucial for assessing tumor burden, whereas tracking individual tumors by aligning scans from multiple time points reveals disease progression. However, these processes remain largely dependent on manual analysis, limiting the accuracy, reproducibility, objectivity, and scalability of tumor characterization. Several deep learning models have enabled automated segmentation and object identification. However, open-source, integrated software platforms that cover the entire workflow - including processing raw CT images, annotating and tracking tumors through time, and generating data reports and visualizations - are still needed. Here, we present LuTuFlow, a computer vision pipeline incorporating a nnU-Net-based deep learning model, configured for murine lung segmentation and tumor analysis. We integrated these modules into a Napari plugin, allowing researchers to apply the entire automated workflow to transform raw CT scan datasets into quantitative readouts and interactive visualizations in a simple graphical user interface. The resulting model, iteratively refined using expert-corrected annotations, generated reliable quantitative estimates of tumor burden.

cancer biology↗

An IL-34-IGF-1 inflammatory axis fuels KRAS-mutant lung cancer progression

Macrophages are innate immune cells of embryonic or adult origin with tissue specific roles in homeostasis, disease surveillance, and wound repair that can be co-opted to promote tumor growth and spread1-11. An understanding of the specific roles of macrophage subsets in lung tumor initiation and progression could promote new therapeutic approaches for this deadly disease. Here, we show that KRASG12D mutations in lung epithelium drive proliferation of resident, embryonically-derived alveolar macrophages, which then promote tumor cell proliferation and protection from ferroptosis, leading to tumor progression. Using genetically engineered mouse models of mutant KRASG12D non-small cell lung cancer12,13, we found that alveolar macrophages accumulate by proliferation in response to tumor cell-secreted IL-34, recapitulating events observed in late embryonic lung development. Tumor alveolar macrophages in turn drive IGF-1-dependent tumor cell proliferation. Neutralization or deletion of IL-34 suppresses IGF-1 expression, reduces macrophage and tumor cell proliferation and inhibits tumor progression. High IL34 and IGF1 correlate with poor survival in KRASG12D/V lung adenocarcinomas and in other solid tumors, indicating that bi-directional proliferative signaling between resident macrophages and tumor cells can drive human lung tumor progression. These studies identify resident macrophage-tumor cell interactions as key interception points for lung cancer therapy.

cancer biology↗

The Immune Landscape of Tumor-Associated Macrophage Reprogramming

Tumor-associated macrophages (TAMs) generally acquire immunosuppressive and tumor-promoting phenotypes, which may contribute to tumor resistance to immunotherapy. We previously showed that suppression of microRNA activity through genetic Dicer1 inactivation rewires TAMs transcriptomes and prompts their immunostimulatory activation. This phenotypic switch enhanced recruitment and activation of CD8+ cytotoxic T cells (CTLs) and improved the efficacy of immunotherapy in mouse cancer models. Here, we performed single-cell RNA sequencing of whole tumors grown in either wild-type mice or mice with macrophage-specific Dicer1 deletion. The analysis of multiple cell populations, including several discrete monocyte and macrophage subsets, indicated broad and convergent immunostimulatory programming of the tumor microenvironment, which was dependent on CTL-derived interferon-gamma (IFN{gamma}), in mice with DICER-deficient macrophages. Intriguingly, dynamic inferences on monocyte/macrophage ontogeny and differentiation by pseudotime analysis revealed trajectories associated with progression into cell cycle, monocyte-to-macrophage differentiation, and transition from an immunostimulatory to an immunosuppressive phenotype in tumors with DICER-proficient macrophages. Dicer1 deficiency interfered with this trajectory and stalled TAMs at an intermediate state between immature monocytes and macrophages with T cell-stimulatory capacity, thereby impeding immunosuppressive TAM development. This translated into enhanced response to antiangiogenic immunotherapy in an immunotherapy-resistant model of non-small cell lung cancer. Cycling/M2-like macrophages were conserved in human melanoma and hepatocellular carcinoma and should represent a more promising therapeutic target than the bulk of TAMs.

cancer biology↗

Identification of the Goliath beetles Fornasinius fornasini Bertoloni and Fornasinius hauseri Kraatz (Scarabaeidae: Cetoniinae)

The Goliath beetles (subtribe Goliathina) are large Cetoniinae comprising a few highly related genera broadly distributed in sub-Saharan Africa. The genus Fornasinius Bertoloni was established in 1853 by Giuseppe Bertoloni to receive a taxon that was sufficiently distinct from the known representatives of the genus Goliathus Lamarck to merit a different placement. In spite of their large size and showy appearance, the members of the genus Fornasinius are poorly known. Here, the type species of the genus, F. fornasini Bertoloni, 1853 (type locality: Mozambique), is identified and re-described. It has emerged that F. fornasini Bertoloni has been misidentified after its original description and that only a few specimens are known of this species. F. fornasini sensu auct. (nec Bertoloni) is instead referable to another taxon, F. hauseri Kraatz, 1896 sp. bon., of which three subspecies can be distinguished: F. hauseri s. str., from south-central Kenya and possibly Cameroon; F. hauseri ssp. hirthi Preiss, 1904 stat. rev., from the Lake Victoria region and northern Tanzania; and a new subspecies to be described from south-east Democratic Republic of the Congo.

zoology↗