Comparison and analysis of the immune landscape at the tumour invasion front in patients with pMMR/MSI-H and pMMR/MSS colorectal cancer.

OBJECTIVES: This study aims to compare and analyse the immune landscape at the tumour invasion front in patients with colorectal cancer (CRC) with proficient mismatch repair (pMMR) and deficient mismatch repair (dMMR). METHODS: A total of 51 patients with CRC were included, comprising 32 patients with pMMR and 19 patients with dMMR. Immunohistochemistry, fluorescence PCR and capillary electrophoresis were used to detect the expression status of MLH1, PMS2, MSH2 and MSH6 proteins to identify patients with pMMR/MSI-H and pMMR/MSS. Multiplex immunofluorescence technology was employed to stain and analyse immune cells at the tumour invasion front. RESULTS: In patients with dMMR CRC, the proportion of CD8⁺ T cells at the tumour invasion front was significantly higher than that in patients with pMMR (26.84% ± 3.17% vs. 6.29% ± 1.62%, p < 0.001), whereas the proportion of CD4⁺ T cells was significantly lower (19.02% ± 2.81% vs. 37.71% ± 3.52%, p < 0.001). Regarding NK cells, the proportion of CD56 bright⁺ cells at the tumour invasion front in patients with dMMR was significantly higher than that in patients with pMMR (6.69% ± 1.04% vs. 1.93% ± 0.48%, p < 0.001). There was no significant difference in the total number of NK cells at the tumour invasion front between the two groups. CONCLUSION: There are significant differences in the infiltration and distribution of immune cells at the tumour invasion front between pMMR/MSI-H and pMMR/MSS CRC. The higher infiltration of CD8⁺ T cells and CD56 bright⁺ cells at the tumour invasion front in patients with dMMR CRC may partly explain their better response to immune therapy. However, these findings require validation in larger cohorts.