Density and location of CD3+ and CD8+ tumor-infiltrating lymphocytes correlate with prognosis of oral squamous cell carcinoma.

Abstract

Tumor-infiltrating lymphocytes (TILs) are regarded as adaptive immune response of the host to cancer cells and valuable prognostic factors. Here, we sought to characterize the densities and locations of CD3+ and CD8+ TILs in primary oral squamous cell carcinoma (OSCC) samples and assess their clinicopathological and prognostic significance. A total number of 169 OSCC samples from 2 independent patient cohorts (Nanjing cohort, 93 cases; Wuxi cohort, 76 cases) were retrospectively collected. The numbers of CD3+ and CD8+ TILs at tumor center (CT) and invasive margin (IM) of OSCC were identified by immunohistochemistry and calculated. The optimal cutoff values for CD3+ and CD8+ TILs to stratify patients were determined by X-tile software in Nanjing cohort and further utilized in Wuxi cohort. The associations between CD3+ /CD8+ TILs and clinicopathological parameters or patient survival were assessed. The prognostic values of CD3+ / CD8+ TILs were evaluated by Cox regression analyses. CD3+ and CD8+ TILs were identified at both CT and IM and enriched at IM. High density of CD3+ TILs at IM (CD3 IM) was significantly associated with increased overall and disease-specific survival (P<.05). High density of CD8+ TILs at CT (CD8 CT) was significantly associated with increased overall but not disease-specific survival. Moreover, CD3 IM and CD8 CT were identified as independent prognostic factors for patient survival. Our findings provide further evidence to support the prognostic values of CD3+ and CD8+ TILs for OSCC, suggesting that TIL subsets might be viable biomarkers and therapeutic targets with translational significance.