| Summary: | Background: Tumor-infiltrating lymphocytes (TILs) have been used to predict the prognosis of solid tumors. In this study, we investigated which molecules in TILs play a role in the prognosis of patients with oral squamous cell carcinoma (OSCC). Methods: In a retrospective case-control study, we immunohistochemically evaluated the expression of CD3, CD8, CD45RO, Granzyme B, and the major histocompatibility complex class I chain-related molecule A (MICA) of the histocompatibility complex as predictors of prognosis in 33 patients with OSCC. The patients were classified as TILs<sup>High</sup> or TILs<sup>Low</sup> according to the number of TILs for each molecule in the central tumor (CT) and invasive margin (IM). Furthermore, MICA expression scores were determined based on the intensity of the staining. Results: CD45RO<sup>+</sup>/TIL in the nonrecurrent group were significantly higher than those in the recurrent group in the CT and IM areas (<i>p</i> < 0.05). The disease-free survival/overall survival rate of the CD45RO<sup>+</sup>/TILs<sup>Low</sup> group in the CT and IM areas and the Granzyme B<sup>+</sup>/TILs<sup>Low</sup> group in the IM area was significantly lower than that of the CD45RO<sup>+</sup>/TILs<sup>High</sup> group and the Granzyme B<sup>+</sup>/TILs<sup>High</sup> group, respectively (<i>p</i> < 0.05). Furthermore, the MICA expression score of tumors around the CD45RO<sup>+</sup>/TILs<sup>High</sup> group was significantly higher than that of the CD45RO<sup>+</sup>/TILs<sup>Low</sup> group (<i>p</i> < 0.05). Conclusions: A high ratio of CD45RO-expressing TILs was associated with a disease-free/overall survival improvement in OSCC patients. Furthermore, the number of TILs that express CD45RO was associated with the expression of MICA in tumors. These results suggest that CD45RO-expressing TILs are useful biomarkers for OSCC.
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