Environmental parameters monitoring in the oldest show cave of Italy: Bossea Cave

Bossea Cave (Piedmont, Italy) was opened to the pubblic in 1874, making it the first show cave of Italy. This cave develops for about 2800 m in a tectonic contact between carbonate rocks of Middle Triassic, and Permotriassic metavolcanics, and it is crossed for about 1.5 km by a subterranean collector. Three different underground laboratories are present inside the cave to monitor and study several environmental parameters: the Underground Karst Laboratory of Bossea Cave managed by the S.O. Bossea C.A.I. and by the DIATI - Politecnico di Torino, the Karst Hydrogeology Lab, financed by the DIATI – Politecnico di Torino, and the “Giovanni Badino” Climatological Research Centre, funded by PaleoLab of DIATI – Politecnico di Torino and S.O. Bossea C.A.I. The Underground Karst Laboratory of Bossea Cave, together with ARPA Piemonte and ARPA Valle d’Aosta, is mainly concerned with the Radon (222Rn) monitoring. The gas exchange dynamics between water, rock and atmosphere are studied: three Radon monitors for water and two for air tracking were installed in different areas of the cave. The Karst Hydrogeology Lab has 11 data acquisition systems to monitor every 15 minutes water levels, temperature and electrical conductivity of the main subterranean collector and a series of secondary water supplies. The flow rate of the main collector and some secondary inputs are recorded since 1982. The “Giovanni Badino” Climatological Research Centre is aimed at monitoring air, rock and water temperature with extremely precise instruments, calibrated by INRiM. Six main stations are located in touristic and non-touristic cave areas. From June 2021, 52 temperature probes are present in the cavity, acquiring data every 10 minutes. Three atmospheric pressure meters, a pluviograph and two data acquisition systems with four probes for CO2 monitoring are part of the same Lab. Caves are the most important geo-heritage worldwide, however, when cavities are transformed in show caves, an additional impact is produced (e.g. air temperature and CO2 increment, lampenflora growth and pollution). Research allows a greater knowledge of the peculiarities and problems of the system, considering the cave not only a tourist attraction, but an important ecosystem to preserve. Bossea cave is a perfect example of how managers, speleologists and scientists collaboration can exist and bring innovation to natural resources conservation

Valorisation et developpement touristique de la Grotta di Bossea (Frabosa Soprana, Cuneo, Italie)

The Bossea Cave has a great interest from the point of view of nature and the environment because many karst and speleogenetic processes are still active. The water stream flowing in the cave was the determining factor of some picturesque morphologies and splendid scenographic effects. An underground laboratory for experimental researches (the “Bossea Scientific Station”) was established in the cave and is operating since 1969 (Biological Section) and 1982 (Physical Section). The cave has been explored and studied since 1850 and opened to the public in 1874. At present its exploitation can be furtherly emphasized. For this purpose a programme was prepared according the following items: 1) rearrangement of the tourist facilities; 2) best exploitation of internal hydrography; 3) creation of alternative trails; 4) improvement of the scientific facilities; 5) creation of new outside facilities; 6) preparation of literature and visual aids. The goals of the Scientific Station installed inside the cave and the results achieved are described by Guido Peano, laboratory director; the cave exploitation project, concerning both the scientific and tourist facilities, is due to Giorgio Fisanotti

THE KARSTOLOGICAL SUBTERRANEAN LABORATORY OF BOSSEA CAVE (N ITALY)

none4noopenVigna, Bartolomeo; Peano, Guido; Villavecchia, Ezechiele; De Waele, JoVigna, Bartolomeo; Peano, Guido; Villavecchia, Ezechiele; De Waele, J

Dataset related to article "High-Resolution Analysis of Mononuclear Phagocytes Reveals GPNMB as a Prognostic Marker in Human Colorectal Liver Metastasis"

<p>This record contains raw data related to article "High-resolution analysis of mononuclear phagocytes reveals GPNMB as a prognostic marker in human colorectal liver metastasis"</p><p><strong>Abstract</strong></p><p>Patients with colorectal liver metastasis (CLM) present with heterogenous clinical outcomes and improved classification is needed to ameliorate the therapeutic output. Macrophages (Mϕ) hold promise as prognostic classifiers and therapeutic targets. Here, stemming from a single-cell analysis of mononuclear phagocytes infiltrating human CLM, we identified two Mϕ markers associated with distinct populations with opposite clinical relevance. The invasive margin of CLM was enriched in pro-inflammatory monocyte-derived Mϕ (MoMϕ) expressing the monocytic marker SERPINB2, and a more differentiated population, tumor-associated Mϕ (TAM), expressing glycoprotein nonmetastatic melanoma protein B (GPNMB). SERPINB2+ MoMϕ had an early inflammatory profile, whereas GPNMB+ TAMs were enriched in pathways of matrix degradation, angiogenesis, and lipid metabolism and were found closer to the tumor margin, as confirmed by spatial transcriptomics on CLM specimens. In a cohort of patients, a high infiltration of SERPINB2+ cells independently associated with longer disease-free survival (DFS; P = 0.033), whereas a high density of GPNMB+ cells correlated with shorter DFS (P = 0.012) and overall survival (P = 0.002). Cell-cell interaction analysis defined opposing roles for MoMϕ and TAMs, suggesting that SERPINB2+ and GPNMB+ cells are discrete populations of Mϕ and may be exploited for further translation to an immune-based stratification tool. This study provides evidence of how multi-omics approaches can identify nonredundant, clinically relevant markers for further translation to immune-based patient stratification tools and therapeutic targets. GPNMB has been shown to set Mϕ in an immunosuppressive mode. Our high dimensional analyses provide further evidence that GPNMB is a negative prognostic indicator and a potential player in the protumor function of Mϕ populations.</p><p> </p&gt

Dataset related to article "High-Resolution Analysis of Mononuclear Phagocytes Reveals GPNMB as a Prognostic Marker in Human Colorectal Liver Metastasis"

<p>This record contains raw data related to article "High-resolution analysis of mononuclear phagocytes reveals GPNMB as a prognostic marker in human colorectal liver metastasis"</p><p><strong>Abstract</strong></p><p>Patients with colorectal liver metastasis (CLM) present with heterogenous clinical outcomes and improved classification is needed to ameliorate the therapeutic output. Macrophages (Mϕ) hold promise as prognostic classifiers and therapeutic targets. Here, stemming from a single-cell analysis of mononuclear phagocytes infiltrating human CLM, we identified two Mϕ markers associated with distinct populations with opposite clinical relevance. The invasive margin of CLM was enriched in pro-inflammatory monocyte-derived Mϕ (MoMϕ) expressing the monocytic marker SERPINB2, and a more differentiated population, tumor-associated Mϕ (TAM), expressing glycoprotein nonmetastatic melanoma protein B (GPNMB). SERPINB2+ MoMϕ had an early inflammatory profile, whereas GPNMB+ TAMs were enriched in pathways of matrix degradation, angiogenesis, and lipid metabolism and were found closer to the tumor margin, as confirmed by spatial transcriptomics on CLM specimens. In a cohort of patients, a high infiltration of SERPINB2+ cells independently associated with longer disease-free survival (DFS; P = 0.033), whereas a high density of GPNMB+ cells correlated with shorter DFS (P = 0.012) and overall survival (P = 0.002). Cell-cell interaction analysis defined opposing roles for MoMϕ and TAMs, suggesting that SERPINB2+ and GPNMB+ cells are discrete populations of Mϕ and may be exploited for further translation to an immune-based stratification tool. This study provides evidence of how multi-omics approaches can identify nonredundant, clinically relevant markers for further translation to immune-based patient stratification tools and therapeutic targets. GPNMB has been shown to set Mϕ in an immunosuppressive mode. Our high dimensional analyses provide further evidence that GPNMB is a negative prognostic indicator and a potential player in the protumor function of Mϕ populations.</p><p> </p&gt

High-Resolution Analysis of Mononuclear Phagocytes Reveals GPNMB as a Prognostic Marker in Human Colorectal Liver Metastasis

Patients with colorectal liver metastasis (CLM) present with heterogenous clinical outcomes and improved classification is needed to ameliorate the therapeutic output. Macrophages (Mϕ) hold promise as prognostic classifiers and therapeutic targets. Here, stemming from a single-cell analysis of mononuclear phagocytes infiltrating human CLM, we identified two Mϕ markers associated with distinct populations with opposite clinical relevance. The invasive margin of CLM was enriched in pro-inflammatory monocyte-derived Mϕ (MoMϕ) expressing the monocytic marker SERPINB2, and a more differentiated population, tumor-associated Mϕ (TAM), expressing glycoprotein nonmetastatic melanoma protein B (GPNMB). SERPINB2+ MoMϕ had an early inflammatory profile, whereas GPNMB+ TAMs were enriched in pathways of matrix degradation, angiogenesis, and lipid metabolism and were found closer to the tumor margin, as confirmed by spatial transcriptomics on CLM specimens. In a cohort of patients, a high infiltration of SERPINB2+ cells independently associated with longer disease-free survival (DFS; P = 0.033), whereas a high density of GPNMB+ cells correlated with shorter DFS (P = 0.012) and overall survival (P = 0.002). Cell–cell interaction analysis defined opposing roles for MoMϕ and TAMs, suggesting that SERPINB2+ and GPNMB+ cells are discrete populations of Mϕ and may be exploited for further translation to an immune-based stratification tool. This study provides evidence of how multi-omics approaches can identify nonredundant, clinically relevant markers for further translation to immune-based patient stratification tools and therapeutic targets. GPNMB has been shown to set Mϕ in an immunosuppressive mode. Our high dimensional analyses provide further evidence that GPNMB is a negative prognostic indicator and a potential player in the protumor function of Mϕ populations

Dataset related to article "Spatial resolution of cellular senescence dynamics in human colorectal liver metastasis"

<p>Dataset related to article "Spatial resolution of cellular senescence dynamics in human colorectal liver metastasis"</p><p><strong>Abstract</strong></p><p>Hepatic metastasis is a clinical challenge for colorectal cancer (CRC). Senescent cancer cells accumulate in CRC favoring tumor dissemination. Whether this mechanism progresses also in metastasis is unexplored. Here, we integrated spatial transcriptomics, 3D-microscopy, and multicellular transcriptomics to study the role of cellular senescence in human colorectal liver metastasis (CRLM). We discovered two distinct senescent metastatic cancer cell (SMCC) subtypes, transcriptionally located at the opposite pole of epithelial (e) to mesenchymal (m) transition. SMCCs differ in chemotherapy susceptibility, biological program, and prognostic roles. Mechanistically, epithelial (e)SMCC initiation relies on nucleolar stress, whereby c- myc dependent oncogene hyperactivation induces ribosomal RPL11 accumulation and DNA damage response. In a 2D pre-clinical model, we demonstrated that RPL11 co-localized with HDM2, a p53-specific ubiquitin ligase, leading to senescence activation in (e)SMCCs. On the contrary, mesenchymal (m)SMCCs undergo TGFβ paracrine activation of NOX4-p15 effectors. SMCCs display opposing effects also in the immune regulation of neighboring cells, establishing an immunosuppressive environment or leading to an active immune workflow. Both SMCC signatures are predictive biomarkers whose unbalanced ratio determined the clinical outcome in CRLM and CRC patients. Altogether, we provide a comprehensive new understanding of the role of SMCCs in CRLM and highlight their potential as new therapeutic targets to limit CRLM progression.</p><p> </p&gt

Intrahepatic CD69+Vδ1 T cells re-circulate in the blood of patients with metastatic colorectal cancer and limit tumor progression

Background More than 50% of all patients with colorectal cancer (CRC) develop liver metastases (CLM), a clinical condition characterized by poor prognosis and lack of reliable prognostic markers. Vδ1 cells are a subset of tissue-resident gamma delta (γδ) T lymphocytes endowed with a broad array of antitumor functions and showing a natural high tropism for the liver. However, little is known about their impact in the clinical outcomes of CLM.Methods We isolated human γδ T cells from peripheral blood (PB) and peritumoral (PT) tissue of 93 patients undergone surgical procedures to remove CLM. The phenotype of freshly purified γδ T cells was assessed by multiparametric flow cytometry, the transcriptional profiles by single cell RNA-sequencing, the functional annotations by Gene Ontology enrichment analyses and the clonotype by γδ T cell receptor (TCR)-sequencing.Results The microenvironment of CLM is characterized by a heterogeneous immune infiltrate comprising different subsets of γδ tumor-infiltrating lymphocytes (TILs) able to egress the liver and re-circulate in PB. Vδ1 T cells represent the largest population of γδ TILs within the PT compartment of CLM that is greatly enriched in Vδ1 T effector (TEF) cells expressing constitutive high levels of CD69. These Vδ1 CD69+ TILs express a distinct phenotype and transcriptional signature, show high antitumor potential and correlate with better patient clinical outcomes in terms of lower numbers of liver metastatic lesions and longer overall survival (OS). Moreover, intrahepatic CD69+ Vδ1 TILs can egress CLM tissue to re-circulate in PB, where they retain a phenotype, transcriptional signature and TCR clonal repertoires resembling their liver origin. Importantly, even the increased frequencies of the CD69+ terminally differentiated (TEMRA) Vδ1 cells in PB of patients with CLM significantly correlate with longer OS. The positive prognostic score of high frequencies of CD69+ TEMRA Vδ1 cells in PB is independent from the neoadjuvant chemotherapy and immunotherapy regimens administered to patients with CLM prior surgery.Conclusions The enrichment of tissue-resident CD69+ Vδ1 TEMRA cells re-circulating at high frequencies in PB of patients with CLM limits tumor progression and represents a new important clinical tool to either predict the natural history of CLM or develop alternative therapeutic protocols of cellular therapies