Immune profile by multiplexed immunohistochemistry associated with recurrence after chemoradiation in rectal cancer

Evidence has emerged that a pretreatment immune profile in rectal cancer is associated with response to chemoradiotherapy (CRT) and recurrence after CRT. However, few studies have evaluated the immune profile differences after CRT regarding recurrence and nonrecurrence.

We included patients with advanced rectal cancer treated with CRT and surgery with recurrence within 1 year in a recurrence group. After sex and age matching with the recurrence group, patients with no recurrence for 3 years after CRT were included in a nonrecurrence group. We extracted the immune profile, including CD3 and CD8, from the surgical specimen after CRT using multispectral fluorescence immunohistochemistry and compared the two groups.

The immune profiles of 65 patients with rectal cancer were assessed; 30 were included in the recurrence group and 35 were included in the nonrecurrence group. CD3⁺ and CD8⁺ T lymphocyte densities were significantly higher in the nonrecurrence group than in the recurrence group (CD3⁺ ; P < 0.001, CD8⁺ ; P = 0.003) in the primary tumor. Consistent results were found in epithelial and stromal cells. Compared with the recurrence group, the distinct profiles of co-expressed immune markers in the nonrecurrence group were revealed (CD3⁺ CD8⁺ , P = 0.001; CD3⁺ CD8⁺ PD-L1^- , P = 0.001; CD3⁺ CD8⁺ FOXP3^- PD-L1^- , P = 0.001).

Vigorous CD3⁺ and CD8⁺ T cell priming post-CRT was prominent in the nonrecurrence group compared with that of the recurrence group. This finding suggests that differences in immune profiles may have clinical significance even after CRT.