Effect of phenotype on outcome in synchronously resected primary colorectal cancer and matched liver metastases.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 221-221
Author(s):  
Kathryn AF Pennel ◽  
Colin William Steele ◽  
Jean A. Quinn ◽  
Antonia K. Roseweir ◽  
Rene Jackstadt ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Poor Prognosis ◽  
Immune Cell ◽  
Primary Tumour ◽  
Tumor Stroma ◽  
Good Prognosis ◽  
Cell Infiltrate ◽  
Primary Tumors ◽  
Immune Cell Infiltrate

221 Background: 5-year survival of patients with resectable colorectal liver metastases is 25-40%. Mechanisms of disease progression are heterogenous and do not follow a clearly defined pathway from genotype to phenotype. In stage I-III colorectal cancer (CRC), patients with high tumor stroma exhibit poor prognosis, while those with high immune cell infiltrate do well following resection. We hypothesise that stromally-dense phenotypes lead to T cell exclusion, myeloid cell accumulation and aggressive metastatic progression. Here, we examine relationships between histological tumor phenotype, cellular infiltrate and outcomes in metastatic CRC. Methods: A unique cohort of synchronously resected primary CRC and matched liver metastases (n = 46) were assessed for immune cell infiltration (CD3, CD4, CD8, CD68, CD66b), inflammatory signalling (CXCR2, PDL-1, MMP9) and hypoxia (CAIX) using immunohistochemistry. Tumors were phenotypically subtyped using immune infiltrate (Klintrup-Makinen Grade (KM)), stromal invasion (tumor-stroma percentage (TSP)) and proliferation (Ki67). Results: Phenotypic subtype of primary tumors was predictive of metastatic subtype (rho = 0.522, p = 0.003). Immune phenotypes were associated with good prognosis and stromal phenotypes with poor prognosis (p = 0.004). Infiltration of macrophages and granulocytes associated with poor outcomes (p = 0.018) and increased CXCR2 expression (p = 0.03) at both sites. Increased CXCR2+ cells and macrophages at both sites associated with stromal phenotype (p = 0.02), tumour budding (p = 0.002), low KM grade (p = 0.05) and poor prognosis (p = 0.002). Macrophage and MMP9 levels increased in metastases compared to primary tumour, but no changes were seen in lymphocyte infiltration, CXCR2 and CD66b. Conclusions: Density of immune cell infiltrate, in the primary and metastatic niche, conferred good prognosis. In contrast, stromal, myeloid rich tumors convey poor prognosis. This clinically relevant and histologically efficient process permits segregation of disease and supports further study of relationships in the tumour microenvironment of CRC in the context of chemotherapy to better target therapeutics to individual patients.

scholarly journals M2 Macrophages Infiltrating Epithelial Ovarian Cancer Express MDR1: A Feature That May Account for the Poor Prognosis

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1224 ◽  
Author(s):  
Susann Badmann ◽  
Sabine Heublein ◽  
Doris Mayr ◽  
Anna Reischer ◽  
Yue Liao ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Drug Resistance ◽  
Epithelial Ovarian Cancer ◽  
Cancer Cells ◽  
Poor Prognosis ◽  
Immune Cell ◽  
M2 Macrophages ◽  
Cell Infiltrate ◽  
Immune Cell Infiltrate ◽  
Mdr1 Expression

Multi drug resistance protein 1 (MDR1) expression on tumor cells has been widely investigated in context of drug resistance. However, the role of MDR1 on the immune cell infiltrate of solid tumors remains unknown. The aim of this study was to analyze the prognostic significance of a MDR1+ immune cell infiltrate in epithelial ovarian cancer (EOC) and to identify the MDR1+ leucocyte subpopulation. MDR1 expression was analyzed by immunohistochemistry in 156 EOC samples. In addition to MDR1+ cancer cells, we detected a MDR1+ leucocyte infiltrate (high infiltrate >4 leucocytes per field of view). Correlations and survival analyses were calculated. To identify immune cell subpopulations immunofluorescence double staining was performed. The MDR1+ leucocyte infiltrate was associated with human epidermal growth factor receptor 2 (HER2) (cc = 0.258, p = 0.005) and tumor-associated mucin 1 (TA-MUC1) (cc = 0.202, p = 0.022) expression on cancer cells. A high MDR1+ leucocyte infiltrate was associated with impaired survival, especially in patients whose carcinoma showed either serous histology (median OS 28.80 vs. 50.64 months, p = 0.027, n = 91) or TA-MUC1 expression (median OS 30.60 vs. 63.36 months, p = 0.015, n = 110). Similar findings for PFS suggest an influence of MDR1+ immune cells on the development of chemoresistance. A Cox regression analysis confirmed the independency of a high MDR1+ leucocyte infiltrate as prognostic factor. M2 macrophages were identified as main part of the MDR1+ leucocyte infiltrate expressing MDR1 as well as the M2 marker CD163 and the pan-macrophage marker CD68. Infiltration of MDR1+ leucocytes, mostly M2 macrophages, is associated with poor prognosis of EOC patients. Further understanding of the interaction of M2 macrophages, MDR1 and TA-MUC1 appears to be a key aspect to overcome chemoresistance in ovarian cancer.

scholarly journals Characterization of immune cell infiltrate in tumor stroma and epithelial compartments in oral squamous cell carcinomas of Sudanese patients

2021 ◽  
Author(s):  
Nuha Mohamed Gaafar ◽  
Tarig Al‐Hadi Osman ◽  
Israa Abdulrahman Ahmed ◽  
Mariam Elsheikh ◽  
Harsh Dongre ◽  
...  
Keyword(s):  
Squamous Cell ◽  
Immune Cell ◽  
Tumor Stroma ◽  
Squamous Cell Carcinomas ◽  
Cell Infiltrate ◽  
Oral Squamous Cell Carcinomas ◽  
Immune Cell Infiltrate

scholarly journals High TKTL1 expression as a sign of poor prognosis in colorectal cancer with synchronous rather than metachronous liver metastases

2020 ◽  
Vol 21 (9) ◽  
pp. 826-831
Author(s):  
Reetta Peltonen ◽  
Kaisa Ahopelto ◽  
Jaana Hagström ◽  
Camilla Böckelman ◽  
Caj Haglund ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Poor Prognosis

scholarly journals Discordance of KRAS Mutational Status between Primary Tumors and Liver Metastases in Colorectal Cancer: Impact on Long-Term Survival Following Radical Resection

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2148
Author(s):  
Francesco Ardito ◽  
Francesco Razionale ◽  
Lisa Salvatore ◽  
Tonia Cenci ◽  
Maria Vellone ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Primary Tumor ◽  
Kras Mutation ◽  
Colorectal Tumor ◽  
Term Survival ◽  
Primary Tumors ◽  
Mutation Status ◽  
Primary Colorectal Tumor ◽  
Kras Mutation Status

If KRAS mutation status of primary colorectal tumor is representative of corresponding colorectal liver metastases (CRLM) mutational pattern, is controversial. Several studies have reported different rates of KRAS discordance, ranging from 4 to 32%. Aim of this study is to assess the incidence of discordance and its impact on overall survival (OS) in a homogenous group of patients. KRAS mutation status was evaluated in 107 patients resected for both primary colorectal tumor and corresponding CRLM at the same institution, between 2007 and 2018. Discordance rate was 15.9%. Its incidence varied according to the time interval between the two mutation analyses (p = 0.025; Pearson correlation = 0.2) and it was significantly higher during the first 6 months from the time of primary tumor evaluation. On multivariable analysis, type of discordance (wild-type in primary tumor, mutation in CRLM) was the strongest predictor of poor OS (p < 0.001). At multivariable logistic regression analysis, the number of CRLM >3 was an independent risk factor for the risk of KRAS discordance associated with the worst prognosis (OR = 4.600; p = 0.047). Results of our study suggested that, in the era of precision medicine, possibility of KRAS discordance should be taken into account within multidisciplinary management of patients with metastatic colorectal cancer.

scholarly journals Immune Cell Infiltration in the Microenvironment of Liver Oligometastasis from Colorectal Cancer: Intratumoural CD8/CD3 Ratio Is a Valuable Prognostic Index for Patients Undergoing Liver Metastasectomy

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1922 ◽  
Author(s):  
Jianhong Peng ◽  
Yongchun Wang ◽  
Rongxin Zhang ◽  
Yuxiang Deng ◽  
Binyi Xiao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Immune Cell ◽  
Cox Regression ◽  
Simultaneous Detection ◽  
Prognostic Index ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Prognostic Information ◽  
Kaplan Meier

Background: A comprehensive investigation into immune cell infiltration provides more accurate and reliable prognostic information for patients with colorectal liver oligometastases (CLO) after liver metastasectomy. Methods: Simultaneous detection of the immune constituents CD3+, CD8+, Foxp3+ T, and α-SMA+ cells in the liver oligometastasis of 133 patients was conducted using a four-colour immunohistochemical multiplex technique. Immune cells were quantified, and tumour-infiltrating lymphocyte (TIL) ratios were subsequently calculated. Correlation analysis was performed using Pearson’s correlation. Recurrence-free survival (RFS) and overall survival (OS) for TIL ratios were analysed using the Kaplan–Meier method and Cox regression models. Results: Significantly fewer CD3+, CD8+, and Foxp3+ T cells were observed in the intratumoural region than in the peritumoural region of liver metastases. CD3+, CD8+, Foxp3+ T, and α-SMA+ cells showed significantly positive correlations with each other both in the intratumoural and peritumoural regions of liver metastases. Only the CD8/CD3 TIL ratio demonstrated a positive correlation between intratumoural and peritumoural regions of liver metastases (r = 0.541, p < 0.001). Patients with high intratumoural CD8/CD3 ratios had significantly longer 3-year RFS (59.0% vs. 47.4%, p = 0.035) and 3-year OS rates (83.3% vs. 65.8%, p = 0.007) than those with low intratumoural CD8/CD3 ratios. Multivariate analyses revealed that the intratumoural CD8/CD3 ratio was independently associated with RFS (HR = 0.593; 95% CI = 0.357–0.985; p = 0.043) and OS (HR = 0.391; 95% CI = 0.193–0.794; p = 0.009). Conclusion: These findings offer a better understanding of the prognostic value of immune cell infiltration on liver oligometastasis from colorectal cancer.

scholarly journals Signaling pathways and immune evasion mechanisms in classical Hodgkin lymphoma

Hematology ◽  
2017 ◽  
Vol 2017 (1) ◽  
pp. 310-316 ◽  
Author(s):  
W. Robert Liu ◽  
Margaret A. Shipp
Keyword(s):  
Hodgkin Lymphoma ◽  
Immune Evasion ◽  
Copy Number ◽  
Genetic Basis ◽  
Immune Cell ◽  
Classical Hodgkin Lymphoma ◽  
Copy Number Alterations ◽  
Cell Infiltrate ◽  
Immune Cell Infiltrate ◽  
Survival And Growth

Abstract Classical Hodgkin lymphoma (cHL) is an unusual B-cell–derived malignancy in which rare malignant Hodgkin and Reed-Sternberg (HRS) cells are surrounded by an extensive but ineffective inflammatory/immune cell infiltrate. This striking feature suggests that malignant HRS cells escape immunosurveillance and interact with immune cells in the cancer microenvironment for survival and growth. We previously found that cHLs have a genetic basis for immune evasion: near-uniform copy number alterations of chromosome 9p24.1 and the associated PD-1 ligand loci, CD274/PD-L1 and PDCD1LG2/PD-L2, and copy number–dependent increased expression of these ligands. HRS cells expressing PD-1 ligands are thought to engage PD-1 receptor–positive immune effectors in the tumor microenvironment and induce PD-1 signaling and associated immune evasion. The genetic bases of enhanced PD-1 signaling in cHL make these tumors uniquely sensitive to PD-1 blockade.

scholarly journals Immune Cell Infiltrate in Chronic-Active Antibody-Mediated Rejection

2020 ◽  
Vol 10 ◽  
Author(s):  
Kasia A. Sablik ◽  
Ekaterina S. Jordanova ◽  
Noelle Pocorni ◽  
Marian C. Clahsen-van Groningen ◽  
Michiel G. H. Betjes
Keyword(s):  
Immune Cell ◽  
Cell Infiltrate ◽  
Antibody Mediated Rejection ◽  
Immune Cell Infiltrate

scholarly journals Signaling pathways and immune evasion mechanisms in classical Hodgkin lymphoma

Blood ◽  
2017 ◽  
Vol 130 (21) ◽  
pp. 2265-2270 ◽  
Author(s):  
W. Robert Liu ◽  
Margaret A. Shipp
Keyword(s):  
Hodgkin Lymphoma ◽  
Immune Evasion ◽  
Copy Number ◽  
Genetic Basis ◽  
Immune Cell ◽  
Classical Hodgkin Lymphoma ◽  
Copy Number Alterations ◽  
Cell Infiltrate ◽  
Immune Cell Infiltrate ◽  
Survival And Growth

Abstract Classical Hodgkin lymphoma (cHL) is an unusual B-cell–derived malignancy in which rare malignant Hodgkin and Reed-Sternberg (HRS) cells are surrounded by an extensive but ineffective inflammatory/immune cell infiltrate. This striking feature suggests that malignant HRS cells escape immunosurveillance and interact with immune cells in the cancer microenvironment for survival and growth. We previously found that cHLs have a genetic basis for immune evasion: near-uniform copy number alterations of chromosome 9p24.1 and the associated PD-1 ligand loci, CD274/PD-L1 and PDCD1LG2/PD-L2, and copy number–dependent increased expression of these ligands. HRS cells expressing PD-1 ligands are thought to engage PD-1 receptor–positive immune effectors in the tumor microenvironment and induce PD-1 signaling and associated immune evasion. The genetic bases of enhanced PD-1 signaling in cHL make these tumors uniquely sensitive to PD-1 blockade.

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