CD8-positive lymphocyte infiltration as a marker of anti-tumor immune response in rectal cancer: pre- and post-neoadjuvant radiotherapy comparison

Abstract

Background

Antitumor immunity, exerted by CD8+ cytotoxic T lymphocytes, plays a vital role in tumor control. Therefore, the present study was conducted to compare the amount of CD8+ tumor-infiltrating lymphocytes (TILs) before and after either long- (LCRT) or short-course radiotherapy (SCRT) in rectal cancer.

Methods

This study retrospectively assessed rectal cancer patients treated by neoadjuvant radiotherapy between 2019 and 2021. Biopsy and surgical samples were subjected to immunohistochemical staining to count CD8+ TILs. The association between the post-to-pre-treatment CD8+ count ratio and treatment groups, histopathological factors, and response to treatment was assessed.

Results

A total of 34 patients were included, with 23 (67.6 %) receiving LCRT and 11 (32.4 %) receiving SCRT. The mean age was 58.56 ± 13.59 years. The number and percentage of CD8+ TILs increased significantly after radiotherapy in all patients (P < 0.001). An increase in CD8+ TILs was observed in both groups, with LCRT showing a median post-to-pre-treatment count ratio of 2.77 and SCRT showing 3.1 (P = 0.127). A generalized linear multivariate model adjusting for mucinous histology, surgical grade, and pathological stages revealed that SCRT was associated with a significantly higher post-to-pre-treatment CD8+ count ratio compared to LCRT (P = 0.03).

Conclusion

Our study highlights that both SCRT and LCRT significantly increase CD8+ TIL count and percentage, reflecting robust immune activation after radiotherapy in rectal cancer, with SCRT showing a higher relative increase, though not statistically significant in unadjusted analyses. After adjusting for histopathological variables, SCRT was independently associated with a greater increase in CD8+ T cells.