The influence of chitinase-3-like protein 1 (YKL-40 or CHI3L1) expression on the immunological properties of the tumor microenvironment, which may affect the effectiveness of immunotherapy, is currently not sufficiently understood in colorectal cancer (CRC). The aim of this study was to investigate the relationship between YKL-40 expression and the immunological properties of the tumor microenvironment in CRC. We performed in silico analysis, including analysis of immune cell infiltration scores and the immune landscape depending on YKL-40 expression, gene set enrichment analysis (GSEA), and analysis of three Gene Expression Omnibus (GEO) datasets. In 48 CRC tissue homogenates and the surgical margin, we analyzed the expression of YKL-40, MMP8, IL17A, and PD-L1. Moreover, we analyzed the expression of YKL-40 in tissue homogenates retrieved from patients with coexisting diabetes, obesity, and smoking. The expression of YKL-40 was significantly higher in CRC tumor tissue compared to healthy tissue and correlated with MMP-8, IL17A, and PD-L1 expression. In silico analysis revealed an association of YKL-40 with disease recurrence, and GSEA revealed a potential link between elevated YKL-40 expression and immunosuppressive properties of the tumor microenvironment in CRC.

The study aimed to assess the expression of B7H3 concerning clinicopathological and histological parameters, including MSI/MSS status, CD-8 cells, tumour-infiltrating lymphocytes (TILs), budding, TNM scale and grading. Moreover, we analyzed the B7H3-related pathways using available online datasets and the immunological context of B7H3 expression, through the 48-cytokine screening panel of cancer tissues homogenates, immunogenic features and immune composition. The study included 158 patients diagnosed with CRC. To assess B7H3 levels, we performed an immunohistochemistry method (IHC) and enzyme-linked immunosorbent assay (ELISA). To elucidate the immune composition of colorectal cancer, we performed the Bio-Plex Pro Human 48-cytokine panel. To study biological characteristics of B7H3, we used online databases. Expression of B7H3 was upregulated in CRC tumour tissues in comparison to adjacent noncancerous margin tissues. The concentrations of B7H3 in tumours were positively associated with T parameter of patients and negatively with tumour-infiltrating lymphocytes score. Additionally, Principal Component Analysis showed that B7H3 expression in tumours correlated positively with cytokines associated with M2-macrophages and protumour growth factors. The expression of B7H3 in tumours was independent of MSI/MSS status. These findings will improve our understanding of B7H3 role in colorectal cancer immunity. Our study suggests that B7-H3 is a promising potential target for cancer therapy. Further studies must clarify the mechanisms of B7H3 overexpression and its therapeutic importance in colorectal cancer.

The study aimed to investigate correlations between HHLA2 levels and parameters, including microsatellite instability (MSI) status, CD8+ cells, and histopathological features: budding, tumor-infiltrating lymphocytes (TILs), TNM scale, grading, cytokines, chemokines, and cell signaling moleculesin colorectal cancer (CRC). Furthermore, the immune infiltration landscape and HHLA2-related pathways in colorectal cancer using available online datasets were analyzed. The study included 167 patients diagnosed with CRC. Expression of HHLA2 was detected by immunohistochemistry method (IHC) and enzyme-linked immunosorbent assay (ELISA). The IHC was used to evaluate the MSI and CD8+ status. The budding and TILs were measured using a light microscope. The concentrations of cytokines, chemokines, and cell signaling molecules were measured to analyze the data by the Bio-Plex Pro Human cytokine screening panel, 48 cytokine assay, and principal component analysis (PCA). Geneset enrichment analysis (GSEA) was conducted to identify HHLA2-related pathways. The biological function of HHLA2 was predicted by Gene Ontology (GO). Analysis of the immune infiltration landscape of HHLA2 in colorectal cancer was made by the web-based tool Camoip. High HHLA2 expression was detected in CRC tumor tissues compared to the adjacent noncancerous tissues. The percentage of HHLA2-positive tumors was 97%. GSEA and GO showed that HHLA2 upregulation correlated with cancer-related pathways and several biological functions. Tumor-infiltrating lymphocytes score correlated positively with IHC HHLA2 expression level percentage. There was a negative correlation between HHLA2, anti-tumor cytokines and pro-tumor growth factors. This study provides a valuable insight into the role of HHLA2 in CRC. We reveal the role of HHLA2 expression as well as a stimulatory and inhibitory immune checkpoint in colorectal cancer. Further research may verify the therapeutic values of the HHLA2-KIR3DL3/TMIGD2 pathway in colorectal cancer.

The immunotherapies based on ICIs in CRC are nowadays limited to microsatellite unstable tumours which are approximately 15% of all CRC cases. There are a few new immune checkpoints belonging to the B7 family, including B7H4. B7H4 expression is associated with so-called "cold tumours", and its function is linked to the downregulation of various immune cell populations. Our study aimed to investigate whether B7H4 expression is dependent on microsatellite status in CRC and on elucidating the immunological context in which the expression of B7H4 occurs. We enrolled 167 patients in the study. We prepared the homogenates from tumour tissues and healthy adjacent tissue to assess the B7H4 levels and the Bio-Plex Pro Human 48-cytokine panel. We assessed the microsatellite status of the tumour, B7H4 expression, CD8+ T cell population, and the TILs and budding in H + E stained slides by the IHC method. We used an online available database for further exploring the biological characteristics of B7H4. The expression of B7H4 was more frequent in microsatellite stable tumours, and was negatively associated with TILs. B7H4 is positively correlated with antitumour immunosuppressive iTME, thus contributing to the immunosuppressive environment in CRC.

Introduction: Osteoprotegerin (OPG), Interleukin-15 (IL-15), and Growth/Differentiation Factor-15 (GDF-15) are all proven to take part in the processes associated with colorectal carcinoma (CRC) including tissue remodeling, inflammation modulation, and metastasis. Aim of the study: To investigate the concentrations of GDF-15, OPG and IL-15 in tumor and margin tissues of CRC in relation to clinicopathological features of patients. Material and methods: The study used 50 specimens of tumor and tumor-free margin tissues obtained from CRC patients. To determine the GDF-15, OPG and IL-15 concentrations commercially available enzyme-linked immunosorbent assay (ELISA) kits were used. Results: Concentrations of GDF-15, OPG and IL-15 were significantly higher in the tumor in comparison with the margin. The tumor levels of GDF-15 were positively associated with those of OPG and IL-15, while tumor levels of OPG correlated positively with those of IL-15. There was no association between levels of investigated molecules and clinical features of patients. Conclusions: The levels of GDF-15, OPG and IL-15 are elevated in patients suffering from CRC. More studies are needed to establish a specific role of these cytokines in the development, tumor growth, progression, and prognosis of CRC and to examine their role as possible CRC treatment candidates.

Introduction: The role of proinflammatory cytokines is said to be crucial in the development of colorectal cancer (CRC). IL-6, IL-23, and chemerin have all been proven to take part in tumor growth and progression. Aim of the study: to determine the level of chemerin and the concentrations of interleukin-6 (IL-6) and interleukin- 23 (IL-23) in the tumor and margin specimens of CRC in relation to histological grade and TNM staging. Material and methods: The study involved 49 samples of tumor and margin tissues obtained from CRC patients. To assess the concentration of chemerin, IL-6, and IL-23, commercially available enzyme-linked immunosorbent assay (ELISA) kits were used. Results: There was no difference in chemerin concentration between the tumor and margin. We found significantly increased levels of IL-6 in tumor tissue compared to margin tissue and higher concentrations of IL-23 in margin tissue than in tumor tissue. Tumor levels of chemerin were significantly correlated with those of IL-23, while its margin concentrations were associated with margin concentrations of IL-6. Additionally, tumor levels of IL-23 were positively correlated with margin levels of IL-6. Conclusions: Chemerin might play an important role in CRC progression through its association with cytokine expression. More studies are needed to investigate the possible role of IL-6, IL-23, and chemerin as potential markers in the development of CRC.