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 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 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.

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Changes in smoking trends and changes in lifestyle, together with worldwide data regarding the incidence of lung cancer in the group of patients with no previous history of smoking, leads to consideration of the differences in the course of the disease, the time of cancer diagnosis, the survival rate, and the occurrence of comorbidities in this group of patients. This study aimed to determine the occurrence of non-smokers among patients undergoing anatomical resection of the lung tissue due to lung carcinoma and to investigate the differences between the course of lung cancer, survival, and the comorbidities in the groups of patients with lung cancer depending on the history of tobacco smoking. The study included a cohort of 923 patients who underwent radical anatomical resection of the lung tissue with lung primary adenocarcinoma or squamous cell carcinoma. The Chi2 Pearson’s test, the t-test, the Mann–Whitney U test, the Kaplan–Meier method, the Log-rank test with Mantel correction, and the Cox proportional hazard model were used for data analysis. We observed a significantly higher mean age of smoking patients compared to the mean age of non-smoking patients. The coexistence of former neoplastic diseases was significantly more frequent in the group of non-smokers compared to the group of smoking patients. We did not observe differences depending on smoking status in the tumor stage, grade, vascular and pleural involvement status in the diagnostic reports. We did not observe differences in the survival between smokers vs. non-smokers, however, we revealed better survival in the non-smoker women group compared to the non-smoker men group. In conclusion, 22.11% of the patients undergoing radical anatomical resection of the lung tissue due to lung cancers were non-smokers. More research on survival depending on genetic differences and postoperative treatment between smokers and non-smokers is necessary.