Analysis of Spatial Organization of Suppressive Myeloid Cells and Effector T Cells in Colorectal Cancer—A Potential Tool for Discovering Prognostic Biomarkers in Clinical Research

Zwing, Natalie; Failmezger, Henrik; Ooi, Chia-Huey; Hibar, Derrek P.; Cañamero, Marta; Gomes, Bruno; Gaire, Fabien; Korski, Konstanty

doi:10.3389/fimmu.2020.550250

Cited by 17 publications

(12 citation statements)

References 29 publications

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“…Regarding mCRC, the immune microenvironment of the liver metastases reflects an important aspect of the overall portrait of the patient's disease, especially the heterogeneity compared to the primary tumor and its clinical impact [ 6 , 7 , 8 , 9 ]. The immune microenvironment of colorectal metastases has not been fully investigated, and published studies are often limited to CD4, CD8, and regulatory T cells [ 10 ]. In addition, several chemotherapy regimens such as oxaliplatin seem to have a preponderant role in antitumor immunologic infiltration, with a stimulating effect on the peritumoral immune response [ 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

Immune microenvironment in patients with mismatch‐repair‐proficient oligometastatic colorectal cancer exposed to chemotherapy: the randomized MIROX GERCOR cohort study

et al. 2022

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In the era of immune checkpoint inhibitors, understanding the metastatic microenvironment of proficient mismatch repair/microsatellite stable (pMMR/MSS) colorectal cancer (CRC) is of paramount importance to both prognostication and the development of more effective novel therapies. In this study, primary and paired metastasis tissue samples were collected from patients with resectable metastatic CRC treated with adjuvant FOLFOX or peri‐operative chemotherapy in the MIROX phase III prospective study. In total, 74 cancer tissues were stained for CD3, CD8, Forkhead box protein 3 (FOXP3), programmed cell death protein‐1 (PD‐1, invasive front, stromal, intra‐epithelial compartments), and programmed death‐ligand 1 (PD‐L1, tumor, immune cells). The immune profiling of primary CRC had a limited value to predict the immune context of paired metastases for all markers but CD3+. The expression of CD8 and PD‐L1 was higher in metastases after neoadjuvant FOLFOX. In metastases, both CD3 T cells at the invasive front and PD‐L1 expressions on immune cells were predictive of better disease‐free survival. These results show that the effect of FOLFOX on modifying the immune microenvironment in resected CRC metastases and measurement of PD‐L1 expression and tumor‐infiltrating CD8 T cells in pMMR/MSS metastatic tissue samples could improve treatment strategies of metastatic CRC patients.

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Section: Introductionmentioning

confidence: 99%

Immune microenvironment in patients with mismatch‐repair‐proficient oligometastatic colorectal cancer exposed to chemotherapy: the randomized MIROX GERCOR cohort study

et al. 2022

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“…According to reports, CD8 + T cells can directly kill tumor cells, including osteosarcoma 50 . Additionally, CD8 + T cells also show a positive prognostic value in stage I–III colon cancer tumors 51 . We found that STC2 and CD8 + T cells showed a significant negative correlation trend, indicating that STC2 promoted the occurrence and development of osteosarcoma by inhibiting CD8 + T cells.…”

Section: Discussionmentioning

confidence: 99%

Five hypoxia and immunity related genes as potential biomarkers for the prognosis of osteosarcoma

Jiang

Zhang

et al. 2022

Sci Rep

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Osteosarcoma accounts for a frequently occurring cancer of the primary skeletal system. In osteosarcoma cells, a hypoxic microenvironment is commonly observed that drives tumor growth, progression, and heterogeneity. Hypoxia and tumor-infiltrating immune cells might be closely related to the prognosis of osteosarcoma. In this study, we aimed to determine the biomarkers and therapeutic targets related to hypoxia and immunity through bioinformatics methods to improve the clinical prognosis of patients. We downloaded the gene expression data of osteosarcoma samples and normal samples in the UCSC Xena database and GTEx database, respectively, and downloaded the validation dataset (GSE21257) in the GEO database. Subsequently, we performed GO enrichment analysis and KEGG pathway enrichment analysis on the data of the extracted osteosarcoma hypoxia-related genes. Through univariate COX regression analysis, lasso regression analysis, multivariate COX regression analysis, etc., we established a predictive model for the prognosis of osteosarcoma. Five genes, including ST3GAL4, TRIM8, STC2, TRPS1, and FAM207A, were found by screening. In particular, we analyzed the immune cell composition of each gene based on the five genes through the CIBERSORT algorithm and verified each gene at the cell and tissue level. Our findings are valuable for the clinical diagnosis and treatment of this disease.

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“…These cells produce high levels of IL-12 and IL-18 cytokines, which are required for type 1 T cell responses, and have been correlated with prolonged survival (65). Further characterization of the specific myeloid cell subpopulations in PSCC is needed and a solution to that problem could be the application of high-dimensional techniques, such as multiplex immunofluorescence and/or imaging mass cytometry, that enable simultaneous spatial analysis of multitude of cell types, which is critical for understanding the tumor-immune system cross-talk (66)(67)(68)(69)(70). Therefore, our group is currently aiming to comprehensively characterize the tumor microenvironment of hrHPV + and hrHPV − PSCC tumors using the above-mentioned highdimensional technologies.…”

Section: Discussionmentioning

confidence: 99%

Distinct Patterns of Myeloid Cell Infiltration in Patients With hrHPV-Positive and hrHPV-Negative Penile Squamous Cell Carcinoma: The Importance of Assessing Myeloid Cell Densities Within the Spatial Context of the Tumor

et al. 2021

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Comprehensive analysis of tumor infiltrating myeloid cells in the tumor microenvironment of penile squamous cell carcinoma (PSCC) is lacking. In this retrospective study, for the first time, PSCC resection specimens (N = 103) were annotated into the following compartments: intratumoral tumor (IT Tumor), intratumoral stroma (IT Stroma), peritumoral tumor (PT Tumor) and peritumoral stroma (PT Stroma) compartments. We then quantified CD14+, CD68+ and CD163+ myeloid cells within these compartments using an image analysis software and assessed their association with various clinical parameters, including high-risk human papillomavirus (hrHPV) status. In the total cohort, hrHPV status, grade of differentiation, age and tumor size were associated with myeloid cell densities. hrHPV+ tumors had higher infiltration rates of CD14+, CD68+ and CD163+ myeloid cells in the IT tumor compartment (p < 0.001, for all) compared to hrHPV− tumors. Furthermore, when examining the association between compartment-specific infiltration and differentiation grade, increased myeloid cell densities in the IT tumor compartment were associated with a more advanced histological grade (p < 0.001, for all). This association remained significant when the hrHPV− cohort (N = 60) was analyzed (CD14+ p = 0.001; CD68+ p < 0.001; CD163+ p = 0.004). Subgroup analysis in the hrHPV+ group (N = 43) showed that high infiltration rates of CD68+ and CD163+ cells in the PT tumor compartment were associated with lymph node (LN) metastasis (p = 0.031 and p = 0.026, respectively). Regarding the association between myeloid cell densities and disease-specific survival, the risk of death was found to decrease slightly as the number of myeloid cells in the IT tumor compartment increased (CD14+ p = 0.04; CD68+ p = 0.05; CD163+ p = 0.02). However, after adjusting for hrHPV, no independent association between myeloid densities and disease-specific survival were found. Altogether, these findings demonstrate the importance of assessing myeloid cell densities within the spatial context of the tumor. Further studies are needed to unravel the specific phenotype of myeloid cells residing in the different compartments, their effect on clinical parameters and the impact of hrHPV on the recruitment of myeloid cell populations in PSCC.

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Analysis of Spatial Organization of Suppressive Myeloid Cells and Effector T Cells in Colorectal Cancer—A Potential Tool for Discovering Prognostic Biomarkers in Clinical Research

Cited by 17 publications

References 29 publications

Immune microenvironment in patients with mismatch‐repair‐proficient oligometastatic colorectal cancer exposed to chemotherapy: the randomized MIROX GERCOR cohort study

Immune microenvironment in patients with mismatch‐repair‐proficient oligometastatic colorectal cancer exposed to chemotherapy: the randomized MIROX GERCOR cohort study

Five hypoxia and immunity related genes as potential biomarkers for the prognosis of osteosarcoma

Distinct Patterns of Myeloid Cell Infiltration in Patients With hrHPV-Positive and hrHPV-Negative Penile Squamous Cell Carcinoma: The Importance of Assessing Myeloid Cell Densities Within the Spatial Context of the Tumor

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