The prognostic role of tumour-infiltrating lymphocytes in oral squamous cell carcinoma: A meta-analysis.

It has been suggested that tumour-infiltrating lymphocytes (TILs) are associated with the progression of oral squamous cell carcinoma (OSCC). However, the prognostic value of TILs is inconclusive due to the heterogeneity of immune cells within the tumour microenvironment. In this meta-analysis, we aimed to assess the prognostic value of TILs in OSCC. The PubMed, Cochrane, Embase, Scopus and Web of Science databases were searched up to April 20, 2019, and 33 studies were ultimately included in this meta-analysis. Our pooled meta-analysis showed that high infiltration of CD8+ TILs, CD45RO+ TILs and CD57+ TILs favoured better overall survival (OS). However, high infiltration of CD68+ macrophages and CD163+ macrophages was associated with poor prognosis in OSCC. These findings suggest that CD8+ TILs, CD45RO+ TILs, CD57+ TILs, CD68+ macrophages and CD163+ macrophages might serve as novel prognostic factors and therapeutic targets in OSCC.

Huang Z ，Xie N ，Liu H ，Wan Y ，Zhu Y ，Zhang M ，Tao Y ，Zhou H ，Liu X ，Hou J ，Wang C ... -  《-》

Prognostic significance of tumor infiltrating immune cells in oral squamous cell carcinoma.

Fang J ，Li X ，Ma D ，Liu X ，Chen Y ，Wang Y ，Lui VWY ，Xia J ，Cheng B ，Wang Z ... -  《BMC CANCER》

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

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.

Zhou C ，Wu Y ，Jiang L ，Li Z ，Diao P ，Wang D ，Zhang W ，Liu L ，Wang Y ，Jiang H ，Cheng J ，Yang J ... -  《-》

High Density of Intratumor CD45RO(+) Memory Tumor-Infiltrating Lymphocytes Predicts Favorable Prognosis in Patients With Oral Squamous Cell Carcinoma.

Although tumor-infiltrating lymphocytes (TILs) have been increasingly appreciated as novel biomarkers for prognostic prediction in cancer, little attention has been paid to the CD45RO+ memory TIL and its associations with clinical outcomes in oral squamous cell carcinoma (OSCC). The purpose of this study was to determine the associations between CD45RO+ TILs and clinicopathologic parameters and prognosis in OSCC. Tissue sections of primary OSCC from 2 independent tertiary referral cancer centers (Nanjing and Wuxi, China) were retrospectively collected and subjected to immunohistochemical staining for CD45RO. Densities of CD45RO+ TILs in the tumor center (CT) and invasive margin were calculated. Optimal cutoff values of CD45RO+ TILs for patient stratification were generated by X-tile software. Kaplan-Meier and Cox regression analyses were performed to assess associations between CD45RO+ TILs and overall survival and recurrence-free survival. Prognostic prediction of CD45RO+ TILs was estimated by receiver operating characteristic (ROC) curve. One hundred sixty-nine eligible patients with OSCC were included. No relevant associations between CD45RO+ TILs and clinicopathologic parameters were identified. Kaplan-Meier analyses indicated that a high density of CD45RO TILs in the CT was significantly associated with favorable overall and recurrence-free survival (P = .0018 and .0007 by log-rank test). Cox proportional regression analyses showed that presence of CD45RO TILs in the CT was an independent prognostic factor for overall survival of OSCC. ROC curves showed that presence of CD45RO TILs in the CT was comparable to clinical stage in predicting patient survival, whereas their combination was superior to either parameter alone. The present findings indicate that intratumor density of CD45RO TILs is a viable and independent prognostic predictor for OSCC.

Zhou C ，Li J ，Wu Y ，Diao P ，Yang J ，Cheng J ... -  《-》

Prognostic Role of CD68(+) and CD163(+) Tumour-Associated Macrophages and PD-L1 Expression in Oral Squamous Cell Carcinoma: A Meta-Analysis.

Background: Oral squamous cell carcinoma (OSCC) is a common malignant cancer in humans. An abundance of tumour associated macrophages (TAMs) create an immunosuppressive tumour microenvironment (TME). TAM markers (CD163 and CD68) are seen to serve as prognostic factors in OSCC. PD-L1 has seen to widely modulate the TME but its prognostic significance remains controversial. The aim of this meta-analysis is to evaluate the prognostic role of CD163+, CD68+ TAMs and PD-L1 in OSCC patients. Methods: Searches in PubMed, Scopus and Web of Science were performed; 12 studies were included in this meta-analysis. Quality assessment of included studies was performed according to REMARK guidelines. Risk of bias across studies was investigated according to the rate of heterogeneity. Meta-analysis was performed to investigate the association of all three biomarkers with overall survival (OS). Results: High expression of CD163+ TAMs were associated with poor overall survival (HR = 2.64; 95% Cl: [1.65, 4.23]; p < 0.0001). Additionally, high stromal expression of CD163+ TAMs correlated with poor overall survival (HR = 3.56; 95% Cl: [2.33, 5.44]; p < 0.00001). Conversely, high CD68 and PD-L1 expression was not associated with overall survival (HR = 1.26; 95% Cl: [0.76, 2.07]; p = 0.37) (HR = 0.64; 95% Cl: [0.35, 1.18]; p = 0.15). Conclusion: In conclusion, our findings indicate CD163+ can provide prognostic utility in OSCC. However, our data suggests CD68+ TAMs were not associated with any prognostic relevance in OSCC patients, whereas PD-L1 expression may prove to be a differential prognostic marker dependent on tumour location and stage of progression.

Chohan MH ，Perry M ，Laurance-Young P ，Salih VM ，Foey AD ... -  《-》