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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. [ABSTRACT FROM AUTHOR]