Simplified and Optimized Immune Score for Colorectal Cancer Microenvironment

Background/Aim: Immunoscore (IS) is an important evaluation method for the tumor immune microenvironment (TIME); however, formal IS analysis requires designated reagents and a specific digital pathology software and image data analysis. This study aimed to investigate whether simplified IS (s-IS) can substitute formal IS upon modifying the location of the assessment of the numbers of immune cells and verify that the addition of T cell subset markers to s-IS can enhance the prognostic impact in patients with colorectal cancer (CRC). Patients and Methods: A total of 82 CRC cases were included in this study. Immunohistochemical analysis was performed using CD3/CD8/CD45RO/FOXP3 on tissue specimens; the expression levels were calculated in the center and perimeter of the tumors using digital pathology. The clinical prognostic significance of the expression of these markers was investigated by concordance index comparison according to their location of assessment and combinations. Results: In the univariate analysis, the CD3, CD8, and FOXP3 levels were significant prognostic factors. Moreover, for each T cell subset marker, the assessment of each T cell subset marker at the tumor perimeter had a stronger prognostic power than that in the tumor center. The modified s-IS (s-IS plus FOXP3 evaluation) was an independent prognostic factor for recurrence-free survival and overall survival through multivariate analysis and demonstrated the best prognostic power compared to other T subset marker combinations. Conclusion: In CRC, TIME evaluation could be simplified by assessing CD3-and CD8-positive T cells in the perimeter of the tumor, and additional FOXP3 evaluation would empower the ability of s-IS evaluation in prognostic assessment.