Colorectal cancer (CRC) is one of the leading cancers in both genders. TNM staging system is still the most commonly used tumor classification and prognostic system. The disadvantage of TNM is that the prognostic information it provides is incomplete, and patients with the same histological tumor stages may differ significantly in the clinical outcome. Therefore, the identification of new prognostic parameters is crucial. The carcinogenic process that gives rise to an individual tumor is unique and tumor microenviroment should be taken into consideration. In CRC, T-cell infiltration is not homogenous, and recent studies are mostly focusing on memory T-cells and CD8 cells in predicting disease-free survival (DFS) and overall survival (OS). It seems that DFS and OS are not only dependent on microsatellite instable or stable status but mostly on the levels of expression of the immune signatures. Also, patients with high infiltration of cytotoxic and memory cells have significantly better outcome. This review consolidates current knowledge and recent research about importance of immune-cell-associated proteins, specific gene profiles of immune cells and immunotherapy in CRC. We also discussed cell-specific signatures in cancer treatment.

• Keywords
• Colorectal cancer (CRC), Genomic profile, Immune cells, Immunotherapy,
• MeSH
• Immunotherapy MeSH
• Immune Checkpoint Inhibitors therapeutic use   MeSH
• Colorectal Neoplasms genetics   immunology   pathology   MeSH
• Humans MeSH
• Tumor Microenvironment MeSH
• Prognosis MeSH
• Sequence Analysis, RNA MeSH
• Neoplasm Staging MeSH
• Computational Biology MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Immune Checkpoint Inhibitors MeSH

One of the most common mechanisms of immune evasion in MSI colorectal cancers (CRCs) is loss of HLA class I expression due to mutations in B2M gene which can become a negative predictor for checkpoint blockade therapy. The aim of this study was the determination of prevalence of B2M somatic mutations in MSI CRC patients and relationship between B2M mutations and lymphocytes infiltration and other clinicopathological features as well as detection of methylation changes in B2M promoter region which can be another mechanism of immune escape. In our study, 37 MSI-H and 5 MSI-L patients were selected for screening of B2M mutational and methylation status. The characterization of patients was based on standard histopathological diagnosis and TNM classification; BRAF, KRAS mutations, tumor-infiltrating lymphocytes and peritumoral lymphoid reaction were also determined. MSI analysis was performed using fragment analysis. B2M mutations were identified by Sanger sequencing, and methylation of CpG islands in promoter region was detected by methylation-specific PCR. Heterozygous mutations in the B2M gene were detected in five MSI-H patients (13.5%), while the mutation c.45_48delTTCT was determined in four patients and mutation c.276delC was found in two patients. One of these five patients was compound heterozygote harboring both mutations. Methylation of the promoter region of the B2M gene was observed in one patient with MSI-H colorectal cancer. Detection of genetic and epigenetic changes in B2M gene could be important in personalized therapy for CRC patients as these changes may be one of the mechanisms of secondary resistance of MSI positive tumors to immunotherapy.

• Keywords
• Beta-2-microglobulin, Cancer immunogenicity, Colorectal cancer, Microsatellite instability, Promoter methylation,
• MeSH
• beta 2-Microglobulin genetics   MeSH
• CpG Islands MeSH
• Adult MeSH
• Down-Regulation MeSH
• Epigenesis, Genetic MeSH
• Colorectal Neoplasms genetics   pathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• DNA Methylation * MeSH
• Microsatellite Instability * MeSH
• Mutation MeSH
• Promoter Regions, Genetic MeSH
• Gene Expression Regulation, Neoplastic MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Neoplasm Staging MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• B2M protein, human MeSH Browser
• beta 2-Microglobulin MeSH