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

作者:Zhou, Chen; Wu, Yaping; Jiang, Lei; Li, Zhongwu; Diao, Pengfei; Wang, Dongmiao; Zhang, Wei; Liu, Laikui; Wang, Yanling; Jiang, Hongbing; Cheng, Jie*; Yang, Jianrong*
来源:Journal of Oral Pathology & Medicine, 2018, 47(4): 359-367.
DOI:10.1111/jop.12698

摘要

BackgroundTumor-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. @@@ MethodsA 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. @@@ ResultsCD3(+) 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. @@@ ConclusionsOur 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.