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

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.