Intratumoral CD3+ and NKp46+ Cells in Colorectal Liver Metastases
Ontology highlight
ABSTRACT:
DISEASE(S): Neoplasm Metastasis,Liver Neoplasms,Colorectal Liver Metastases
PROVIDER: 2203151 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
Similar Datasets
Project description:More than 50% of all patients with colorectal cancer (CRC) develop liver metastasis (CLM) that are characterized by poor prognosis and lack of reliable prognostic markers. Vd1 T cells are gd T innate-like lymphocytes endowed with a broad array of antitumor functions at peripheral tissues, but little is known about their impact in the pathophysiology of CLM. We assessed the phenotype and functions by flow cytometry, clonotype by gdTCR-sequencing, transcriptional profiles by single cell RNA-sequencing and clinical impact of human Vd1 T cells isolated from peripheral blood (PB), tumor-free liver parenchyma surrounding CLM (TFLP) and metastatic tumor (MT) from a large cohort of CLM patients. We show here that CLM tissue is highly enriched of CD69+ Vd1 T effector (TEF) cells in the TFLP area. These cells have a peculiar phenotype, high anti-tumour potential and correlate with a better clinical outcome in terms of lower numbers of liver metastatic lesions and longer overall survival (OS). Moreover, the specific terminally differentiated (TEMRA) CD69+ Vd1 cells can egress CLM tissue to re-circulate in the bloodstream, where they retains high effector functions and show phenotypic/transcriptional and gdTCR profiles that resemble their liver origin. Importantly, high frequencies of CD69+TEMRA Vd1 cells in PB predict a longer OS of CLM patients that is not affected by the neo-adjuvant chemotherapy/immunotherapy regimens administered to CLM patients. The presence at high frequencies of liver memory CD69+TEMRA Vd1 cells in CLM homing to PB represents a new important target to better predict CLM clinical outcomes and to develop novel protocols of adoptive cell transfer therapies.
2023-10-03 | GSE159051 | GEO
Project description:The immune landscape impacts outcome and therapeutic response in many tumor types, including colorectal liver metastases (CLM). It has long been known that in vitro polarized macrophages differ in morphology. Here we tested the hypothesis that morphology of tumor-associated macrophages (TAMs) in CLM represents a correlate of function with prognostic significance. Density and morphological metrics (area and perimeter) of TAMs were measured and correlated with clinic-pathological prognostic variables. While density of TAMs did not correlate with survival of CLM patients, cell area identified small and large macrophages that associated with 5-year disease-free survival rate of 27.8% and 0.2% respectively (P<0.001). RNA sequencing of morphologically distinct macrophages identified LXR/RXR as the most enriched pathway in large macrophages and upregulation of genes involved in cholesterol metabolism, phagocytosis and downregulation of the inflammatory program. These results support that accurate, morphometric characterization can serve as a simple readout of TAM diversity with prognostic significance.
2020-08-05 | GSE131353 | GEO
Project description:The performance of multiple minor hepatectomies (MMH) instead of major hepatectomies (MH) in patients with colorectal liver metastases (CLM) is object of debate. We build a study, using the propensity score matched analysis, to compare the short- and long-term outcome of the tow groups of patients.
| 2181400 | ecrin-mdr-crc
Project description:PURPOSE: We sought to identify genes of clinical significance to predict survival and the risk for colorectal liver metastasis (CLM), the most common site of metastasis from colorectal cancer (CRC). PATIENTS AND METHODS: We profiled gene expression in 31 specimens from primary CRC and 32 unmatched specimens of CLM, and performed Significance Analysis of Microarrays (SAM) of the expressed genes between these two groups. To characterize the clinical relevance of two highly-ranked differentially expressed signature genes, we analyzed the expression of secreted phosphoprotein 1 (SPP1 or osteopontin) and lymphoid enhancer factor-1 (LEF1) by immunohistochemistry using a tissue microarray (TMA) representing an independent set of 154 patients with primary CRC. Supervised analysis using SAM identified 963 genes with significantly higher expression in CLM compared to primary CRC, with a false discovery rate of <0.5%. TMA analysis showed SPP1 and LEF1 protein overexpression in 60% and 44% of CRC cases, respectively. Subsequent occurrence of CLM was significantly correlated with the overexpression of LEF1 (chi-square p = 0.035), but not SPP1 (p = 0.14). Kaplan Meier analysis revealed significantly worse survival in patients with overexpression of LEF1 (p < 0.01), but not SPP1 (p = 0.11). Both univariate and multivariate analyses identified stage (p < 0.0001) and LEF1 overexpression (p < 0.05) as important prognostic markers, but not tumor grade or SPP1. CONCLUSION: Among signature genes differentially expressed between CLM and primary CRC, we demonstrate overexpression of LEF1 in primary CRC to be a prognostic factor for poor survival and increased risk for liver metastasis. cDNA microarrays from the Stanford Functional Genomics Facility were used to perform mRNA transcript profiling of 31 freshly-frozen primary colorectal cancer specimens, and compared to published profiles of 32 unmatched colorectal liver metastases and 12 normal liver specimens.
2011-03-22 | E-GEOD-22834 | biostudies-arrayexpress
Project description:PURPOSE: We sought to identify genes of clinical significance to predict survival and the risk for colorectal liver metastasis (CLM), the most common site of metastasis from colorectal cancer (CRC). PATIENTS AND METHODS: We profiled gene expression in 31 specimens from primary CRC and 32 unmatched specimens of CLM, and performed Significance Analysis of Microarrays (SAM) of the expressed genes between these two groups. To characterize the clinical relevance of two highly-ranked differentially expressed signature genes, we analyzed the expression of secreted phosphoprotein 1 (SPP1 or osteopontin) and lymphoid enhancer factor-1 (LEF1) by immunohistochemistry using a tissue microarray (TMA) representing an independent set of 154 patients with primary CRC. Supervised analysis using SAM identified 963 genes with significantly higher expression in CLM compared to primary CRC, with a false discovery rate of <0.5%. TMA analysis showed SPP1 and LEF1 protein overexpression in 60% and 44% of CRC cases, respectively. Subsequent occurrence of CLM was significantly correlated with the overexpression of LEF1 (chi-square p = 0.035), but not SPP1 (p = 0.14). Kaplan Meier analysis revealed significantly worse survival in patients with overexpression of LEF1 (p < 0.01), but not SPP1 (p = 0.11). Both univariate and multivariate analyses identified stage (p < 0.0001) and LEF1 overexpression (p < 0.05) as important prognostic markers, but not tumor grade or SPP1. CONCLUSION: Among signature genes differentially expressed between CLM and primary CRC, we demonstrate overexpression of LEF1 in primary CRC to be a prognostic factor for poor survival and increased risk for liver metastasis.
2011-03-22 | GSE22834 | GEO
Project description:Colorectal liver metastases (CLM) are currently considered an absolute contraindication for liver transplantation (Lt) although Lt for other primary and secondary liver malignancies show excellent outcome in selected patients. Before 1995, several Lts for CLM were performed, but the outcome was poor (18% 5-year survival) and Lt for CLM was stopped. Since then, several advances have been achieved and survival following Lt has improved by almost 30%. Thus, a 5-year survival of about 50% following Lt for CLM could be anticipated.
The investigators have previously included 21 patients in a pilot study. All patients had advanced CLM at the time of Lt. Long term overall survival (OS) exceeds by far previously reported outcome for this patient group and is comparable or better than survival following repeat Lt for non-malignant diagnoses. Development of robust selection criteria may further improve the results.
The investigators will conduct a randomized controlled trial to explore whether liver transplantation in selected patients with liver metastases from CRC can obtain significant life extension and better health related quality of life compared to patients receiving surgical resection.
The investigators will also explore if patient selection according to nomo-grams for outcome of colorectal cancer can define a subgroup of patients with a 5 year survival of at least 50% or even cure from the disease.
| 2116273 | ecrin-mdr-crc
Project description:Plants defend themselves against herbivores by activating a plethora of genetic and biochemical mechanisms aimed at reducing plant damage and insect survival. The short-term plant response to insect attack is well understood, but less is known about the maintenance of this response over time. We performed transcriptomic and metabolomics analyses in order to identify genes and metabolites involved in the long-term response of maize to attack by the corn borer Sesamina nonagrioides. To determine the role of elicitors present in caterpillar secretions, we also evaluated the response of maize stem challenged with insect regurgitates. The integrative analysis of the omics results revealed that the long-term response in maize is characterized by repression of the primary metabolism and a strong redox response, mainly mediated by germin-like proteins to produce anti-nutritive and toxic compounds that reduce insect viability, and with the glutathione–ascorbate cycle being crucial to minimize the adverse effects of reactive oxygen species (ROS) on the plant. Our results suggest that different defense mechanisms are involved in the long-term response compared to those reported during the early response. We also observed a marginal effect of the caterpillar regurgitates on the long-term defensive response.
2020-07-14 | MSV000085753 | GNPS
Project description:Salt tolerance in grapevine is associated with the exclusion of chloride ions (ClM-bM-^@M-^S) from the shoot. The rate-limiting step for this process has been identified as the passage of ClM-bM-^@M-^S between the root symplast and the xylem apoplast through membrane integral proteins. To identify candidate genes for these proteins we used a custom microarray to compare the root transcriptomes of three grapevine varieties (Vitis spp.) that differ in their capacity to exclude ClM-bM-^@M-^S from shoots. When challenged with 50 mM ClM-bM-^@M-^S there were transcriptional responses that differed across the rootstocks 140 Ruggeri (a good ClM-bM-^@M-^S excluder) and K51-40 (a poor ClM-bM-^@M-^S excluder), and Cabernet Sauvignon (an intermediate ClM-bM-^@M-^S excluder and Vitis vinifera control). The magnitude of these salt-induced changes correlated with the amount of ClM-bM-^@M-^S accumulated in shoots. Abiotic-stress responsive transcripts (e.g. heat shock proteins) were induced in 140 Ruggeri. Respiratory transcripts were repressed in Cabernet Sauvignon. Expression of hypersensitive response and ROS scavenging transcripts were altered in the sensitive K51-40. Despite these differences, no obvious candidate ClM-bM-^@M-^S transporters were identified from the salt treatment. In contrast, under control conditions where differences in shoot ClM-bM-^@M-^S exclusion between rootstocks were still significant, we identified a number of genes encoding putative ion channels including VvSLAH3, VvALMT1, and possible regulators of these proteins such as VvSnRK2.6 and calcium dependent protein kinases (CDPK) as being differentially expressed between rootstocks. Members of the low affinity nitrate transporter (NRT1), and chloride channel (CLC) families were also identified. We propose these as useful candidates for further study within breeding programs aimed at improving plant salt tolerance in grapevine and other crops. Comparative: genotype versus genotype (control); and control (0 mM Cl) versus salt (50 mM Cl). Rooted leaves were grown as described by Gong et. al. (2010) (Journal of Experimental Botany). After 2 weeks of hydroponic growth, plants were exposed to 0 mM or 50 mM chloride stress for 4 days. Three biological replicates were used for 140 Ruggeri. Four biological replicates were used for Cabernet Sauvignon. Four biological replicates were used for K51-40. Each biological replicate consisted of total roots from four individual plants pooled together.
2014-09-30 | E-GEOD-57770 | biostudies-arrayexpress
Project description:Immune cells that infiltrate a tumor may be a prognostic factor for patients who have had surgically resected hepatocellular carcinoma (HCC). The density of intratumoral total (CD3(+)) and cytotoxic (CD8(+)) T lymphocytes was measured in the tumor interior and in the invasive margin of 65 stage I to IV HCC tissue specimens from a single cohort. Immune cell density in the interior and margin was converted to a binary score (0, low; 1, high), which was correlated with tumor recurrence and relapse-free survival (RFS). In addition, the expression of programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) was correlated with the density of CD3(+) and CD8(+) cells and clinical outcome. High densities of both CD3(+) and CD8(+) T cells in both the interior and margin, along with corresponding Immunoscores, were significantly associated with a low rate of recurrence (P = 0.007) and a prolonged RFS (P = 0.002). In multivariate logistic regression models adjusted for vascular invasion and cellular differentiation, both CD3(+) and CD8(+) cell densities predicted recurrence, with odds ratios of 5.8 [95% confidence interval (CI), 1.6-21.8] for CD3(+) and 3.9 (95% CI, 1.1-14.1) for CD8(+) Positive PD-L1 staining was correlated with high CD3 and CD8 density (P = 0.024 and 0.005, respectively) and predicted a lower rate of recurrence (P = 0.034), as well as prolonged RFS (P = 0.029). Immunoscore and PD-L1 expression, therefore, are useful prognostic markers in patients with HCC who have undergone primary tumor resection. Cancer Immunol Res; 4(5); 419-30. ©2016 AACR.
| S-EPMC5303359 | biostudies-literature