Tumor microenvironment classification based on T-cell infiltration and PD-L1 in patients with mismatch repair-proficient and -deficient colorectal cancer

The classification of tumor microenvironments according to the presence or absence of tumor infiltrating lymphocytes (TILs) and programmed death ligand-1 (PD-L1) expression has been used to predict the efficacy of immune checkpoint inhibitor antibodies in several cancer types, not including colorectal cancer (CRC). The current study investigated the TIL/PD-L1 status of patients with CRC, particularly patients who presented as mismatch repair-proficient (pMMR) and mismatch repair-deficient (dMMR). A total of 243 patients with CRC were enrolled and defined as pMMR (121 patients) or dMMR (122 patients). Using Pearson's χ² test and multivariable multinomial logistic regression analysis, the associations between MMR status, TIL presence and PD-L1 expression were investigated, in addition to the association between TIL/PD-L1 status and clinicopathological features. The results demonstrated that the dMMR group more frequently exhibited TIL⁺ (85/122 vs. 61/121) and PD-L1⁺ (49/122 vs. 32/121) phenotypes compared with the pMMR group. PD-L1⁺ expression was identified in 42.4% of TIL⁺ cases in the dMMR group, while only 18.0% of TIL⁺ cases were PD-L1⁺ in the pMMR group. High programmed death-1 expression and dMMR status were revealed as two independent risk factors for TIL⁺ PD-L1⁺ status. In conclusion, compared with the pMMR group, the dMMR group was more likely to present with a TIL⁺ PD-L1⁺ status, which suggests that a TIL⁺ PD-L1⁺ tumor microenvironment may partly contribute to the improved response of dMMR patients to anti-PD-1/L1 therapy.