scholarly journals Correction to: Interplay of stromal tumor-infiltrating lymphocytes, normal colonic mucosa, cancer-associated fibroblasts, clinicopathological data and the immunoregulatory molecules of patients diagnosed with colorectal cancer

2021 ◽  
Author(s):  
Łukasz Zadka ◽  
Mariusz Chabowski ◽  
Damian Grybowski ◽  
Aleksandra Piotrowska ◽  
Piotr Dzięgiel
Keyword(s):  
Colorectal Cancer ◽  
Colonic Mucosa ◽  
Tumor Infiltrating Lymphocytes ◽  
Stromal Tumor ◽  
Normal Colonic Mucosa ◽  
Cancer Associated Fibroblasts ◽  
Infiltrating Lymphocytes

scholarly journals Interplay of stromal tumor-infiltrating lymphocytes, normal colonic mucosa, cancer-associated fibroblasts, clinicopathological data and the immunoregulatory molecules of patients diagnosed with colorectal cancer

2021 ◽  
Author(s):  
Łukasz Zadka ◽  
Mariusz Chabowski ◽  
Damian Grybowski ◽  
Aleksandra Piotrowska ◽  
Piotr Dzięgiel
Keyword(s):  
Colorectal Cancer ◽  
Negative Correlation ◽  
Colonic Mucosa ◽  
Tnm Classification ◽  
Stage Iv ◽  
Tumor Infiltrating Lymphocytes ◽  
Tumor Stroma ◽  
Lymphocytic Infiltration ◽  
Normal Colonic Mucosa ◽  
Ki 67

AbstractA total of 94 patients with colorectal cancer (CRC) were included in this study. Lymphocytic infiltration of CD45+ cells in the normal colon was more pronounced than that in the paired tumor stroma (p = 0.0008). The mean immunoscore of CD45+TILs was decreased in CRC compared with the controls (p = 0.0010). The percentage of CD3+ cells was higher in stage II than in stage IV (p = 0.0218) and showed a negative correlation with the TNM classification (r = -0.2867, p = 0.0109). The number of stromal CD4+TILs was higher in stage I than in stage III (p = 0.0116) and IV (p = 0.0104), and there was a negative correlation between this number and the stage (r = -0.3708, p = 0.0008). There was a positive correlation between the Ki-67 and CD45+ (r = 0.2468, p = 0.0294), CD3+ (r = 0.3822, p = 0.0006), and CD4+ cells (r = 0.5465, p < 0.0001). The levels of cancer-associated fibroblast (CAF) markers such as α-SMA, thrombin and fibronectin were significantly higher in CRC than in normal colonic mucosa. The immunohistochemical expression of α-SMA was negatively correlated with TILs, while fibronectin showed positive coexpression. A higher number of cells expressing IL-2Rα, PD-L1, CD33 and CD14 were found in colorectal adenocarcinomas than in controls. The number of CD14+ cells was also dependent on the TNM stage (p = 0.0444) and tumor budding (p = 0.0324). These findings suggest a suppressive impact of CRC on the adaptive immune response and emphasize the importance of CAFs in regulating tumor immunity.

scholarly journals Identification of biomarkers related to Tumor-Infiltrating Lymphocytes (TILs) infiltration with gene co-expression network in colorectal cancer

Bioengineered ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 1676-1688
Author(s):  
Rong Liao ◽  
Qi-Zhi Ma ◽  
Cong-Ya Zhou ◽  
Jun-Jun Li ◽  
Ning-Na Weng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Infiltrating Lymphocytes ◽  
Infiltrating Lymphocytes

Tumor-Infiltrating FOXP3+ T Regulatory Cells Show Strong Prognostic Significance in Colorectal Cancer

2009 ◽  
Vol 27 (2) ◽  
pp. 186-192 ◽  
Author(s):  
Paul Salama ◽  
Michael Phillips ◽  
Fabienne Grieu ◽  
Melinda Morris ◽  
Nik Zeps ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colonic Mucosa ◽  
Tumor Tissue ◽  
Early Stage ◽  
Prognostic Significance ◽  
High Density ◽  
Prognostic Indicators ◽  
Normal Colonic Mucosa ◽  
Solid Cancer ◽  
Histopathologic Features

Purpose To determine the prognostic significance of FOXP3+ lymphocyte (Treg) density in colorectal cancer compared with conventional histopathologic features and with CD8+ and CD45RO+ lymphocyte densities. Patients and Methods Tissue microarrays and immunohistochemistry were used to assess the densities of CD8+, CD45RO+, and FOXP3+ lymphocytes in tumor tissue and normal colonic mucosa from 967 stage II and stage III colorectal cancers. These were evaluated for associations with histopathologic features and patient survival. Results FOXP3+ Treg density was higher in tumor tissue compared with normal colonic mucosa, whereas CD8+ and CD45RO+ cell densities were lower. FOXP3+ Tregs were not associated with any histopathologic features, with the exception of tumor stage. Multivariate analysis showed that stage, vascular invasion, and FOXP3+ Treg density in normal and tumor tissue were independent prognostic indicators, but not CD8+ and CD45RO+. High FOXP3+ Treg density in normal mucosa was associated with worse prognosis (hazard ratio [HR] = 1.51; 95% CI, 1.07 to 2.13; P = .019). In contrast, a high density of FOXP3+ Tregs in tumor tissue was associated with improved survival (HR = 0.54; 95% CI, 0.38 to 0.77; P = .001). Conclusion FOXP3+ Treg density in normal and tumor tissue had stronger prognostic significance in colorectal cancer compared with CD8+ and CD45RO+ lymphocytes. The finding of improved survival associated with a high density of tumor-infiltrating FOXP3+ Tregs in colorectal cancer contrasts with several other solid cancer types. The inclusion of FOXP3+ Treg density may help to improve the prognostication of early-stage colorectal cancer.

Association of KMT2C/D loss-of-function mutations with tumor infiltrating lymphocytes and response to immune checkpoint inhibitors in solid tumors.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2587-2587
Author(s):  
Ruiqi Liu ◽  
Yanling Niu ◽  
Xin Zhang ◽  
Tonghui Ma
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
T Cells ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Tumor Infiltrating Lymphocytes ◽  
Loss Of Function ◽  
Cancer Types ◽  
Immune Related Genes ◽  
Infiltrating Lymphocytes

2587 Background: Dysregulation of HMTs plays an important role in tumorigenesis. KMT2C and KMT2D are enzymatically active scaffold proteins that form the core of mammalian COMPASS complexes, which methylate the histone 3 lysine 4. Both KMT2C and KMT2D are involved in the regulation of gene expression. Therefore, we explored the associations of KMT2C/D loss-of-function (LOF) mutations with the expression of immune-related genes, the levels of tumor infiltrating lymphocytes (TILs), and response to immune checkpoint inhibitors (ICIs). Methods: KMT2C/D LOF mutations were defined as nonsense, frameshift, splice site variants within consensus regions, start lost, and stop lost/gained variants. An ICIs treatment cohort from the MSKCC was used for exploring the associations between KMT2C/D LOF mutations and ICIs efficacy. The RNA-Seq data obtained from the TCGA cohort was used for analysis of gene expression and the levels of TILs using CIBERSORT. Results: In MSKCC pan-cancer dataset, patients with KMT2C/D LOF mutations had a relatively longer median overall survival (OS) compared to those with non-LOF mutations, although the result did not reach statistical significance (P = 0.0832). Then we analyzed the predictive roles of KMT2C/D LOF mutations for each cancer type. The results showed that the predictive role of KMT2C/D LOF mutations for the clinical efficacy of ICIs therapy was only observed in colorectal cancer (P = 0.045). However, we did not find the associations of KMT2C/D LOF mutations with ICIs efficacy in bladder cancer, breast cancer, melanoma, glioma, head and neck cancer, renal cell carcinoma, NSCLC, and esophagogastric cancer. Consistently, analysis of TILs in colorectal cancer revealed that KMT2C/D LOF was associated with increased infiltration of several types of immune cells, such as CD8+ T cells (P = 0.0001), activated NK cells (P = 0.0001), M1 macrophage (P = 0.0005), M2 macrophage (P = 0.0115), and neutrophils (P = 0.0209). Meanwhile, regulatory T cells (Tregs) (P = 0.0048) and M0 macrophage (P = 0.0043) were dramatically decreased in KMT2C/D LOF group for colorectal cancer. Moreover, there were no significant relationships between KMT2C/D LOF and the levels of TILs in other cancer types. Our data also demonstrated that KMT2C and KMT2D could regulate the expression of more than 30 immune-related genes in colorectal cancer. Conclusions: Our data indicated that KMT2C/D LOF mutations were significantly correlated with better outcomes of ICIs therapy in colorectal cancer, suggesting it can be as a useful predictor for response to ICIs in colorectal cancer. Meanwhile, we found the associations of KMT2C/D LOF with the levels of TILs in colorectal cancer, but not in other cancer types, indicating that the efficacy of ICIs was consistent with the levels of TILs.

The different immune profiles of normal colonic mucosa in cancer-free Lynch syndrome carriers and Lynch syndrome colorectal cancer patients

2021 ◽  
Author(s):  
Lena Bohaumilitzky ◽  
Klaus Kluck ◽  
Robert Hüneburg ◽  
Richard Gallon ◽  
Jacob Nattermann ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lynch Syndrome ◽  
Cancer Patients ◽  
Colonic Mucosa ◽  
Normal Colonic Mucosa ◽  
Colorectal Cancer Patients

scholarly journals Prediction of Benefit from Checkpoint Inhibitors in Mismatch Repair Deficient Metastatic Colorectal Cancer: Role of Tumor Infiltrating Lymphocytes

2020 ◽  
Vol 25 (6) ◽  
pp. 481-487 ◽  
Author(s):  
Fotios Loupakis ◽  
Ilaria Depetris ◽  
Paola Biason ◽  
Rossana Intini ◽  
Alessandra Anna Prete ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Mismatch Repair ◽  
Checkpoint Inhibitors ◽  
Tumor Infiltrating Lymphocytes ◽  
Infiltrating Lymphocytes
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