Development and validation of a seven‐immune‐feature‐based prognostic score for oral squamous cell carcinoma after curative resection

Abstract

Immune infiltrates have been increasingly recognized as robust prognostic factors for human cancer. Here, we developed and validated a seven‐immune‐feature‐based prognostic score (7IFBPS) for patients with oral squamous cell carcinoma (OSCC) after curative resection. Fourteen immune features regarding detailed locations and densities of seven types of tumor‐infiltrating immune cells (TIIs) were characterized in clinical samples from 269 eligible patients in three independent cohorts by immunohistochemistry coupled with digital quantitation. Optimal cutoff values for individual immune features were yielded using X‐tile software. The 7IFBPS was constructed by Kaplan–Meier and Cox regression model in training cohort and verified in testing, validation and combined cohorts. Concordance index (C‐index), receiver operating characteristics and calibration curves were employed to define the performance of 7IFBPS in prognostic prediction. High CD3 IM (invasive margin), CD3 CT (center of tumor), CD8 CT, CD45RO IM, CD45RO CT, FOXP3 IM and FOXP3 CT significantly associated with improved survival. The 7IFBPS score was calculated using the formula: 1.041 × CD3 IM + 1.24 × CD3 CT + 1.701 × CD8 CT + 1.127 × CD45RO IM + 1.348 × CD45RO CT + 1.089 × FOXP3 IM + 1.483 FOXP3 CT. High 7IFBPS significantly associated with improved survival in all cohorts and served as an independent prognostic predictor. The C‐index of 7IFBPS for predicting survival was 0.668 (95% CI, 0.609–0.726). Calibration curves for survival probability showed good agreement between prediction by 7IFBPS and actual observation. Collectively, our findings established the 7IFBPS as a novel powerful prognostic classifier for resectable OSCC. It holds potentials to be incorporated into current prognostic regime to better patient stratification.

Prognostic role of CD11b+ myeloid-derived suppressor cells in oral squamous cell carcinoma

“…1 Although various genetic or epigenetic biomarkers in OSCC have been proposed for prognostic assessment including microRNA, lncRNA and alternative mRNA splicing signature, they are still far from optimal. 20,22,23 In addition to these intrinsic features of cancer itself, tumor-infiltrating immunocytes have been established as key drivers underlying tumorigenesis as well as novel biomarkers with tremendous diagnostic and prognostic significance. 4,6 Here, we determined the location and amount of MDSCs in OSCC and revealed that high amount of CD11b + MDSCs associated with inferior survival and quantification of CD11b + MDSCs might be a novel independent prognostic factor for OSCC.…”

“…16,17 The density of CD11b + MDSCs in OSCC specimens was recorded independently at CT and IM and presented as the mean of positively stained cells per mm 2 , similar to our previous report. [18][19][20] As shown in Figure 1, cell counts of CD11b + MDSCs were automatically quantified using ImageJ (version 2.0). The optimal cut-off values for the densities of CD11b + MDSCs at CT and IM were determined after analyzing the association between cell amount and overall survival (OS) by X-tile software with a minimum P value approach (version 3.6.1, https://medicine.yale.edu/lab/rimm/research/software/).…”

Immunoscore Combining CD8, FoxP3 and CD68 Expression and Distribution Predicts the Prognosis of Head and Neck Cancer Patients

“…In two studies, immunoscore only included TILs, and more precisely CD3 + and CD8 + cells (Lechner et al 2017;Zhang et al 2018). A recent study con rmed the positive prognostic impact of TILs in oral squamous cell carcinomas by increasing the immune signature to seven markers that can predict patient survival (Zhou et al 2020).…”

Biomarkers for Immunotherapy of Oral Squamous Cell Carcinoma: Current Status and Challenges

“…For oral carcinoma, identification of immune feature-based prognostic score has been recently introduced by Zhou et al. ( 38 ) who reported a promising prognostic value for an immunoscore based on the evaluation of CD3 in central areas and at invasive margins of OSCC; CD8, CD45RO, and FOXP3 in the central part of OSCC; FOXP3 and CD45RO at invasive margins of OSCC. However, the proposed immunoscore for OSCC will require further validation.…”

“…The most promising results with immunoscore have been reported in colorectal cancer where a scoring system for the quantification of CD3 and CD8 were standardized and showed a promising predictive power superior to TNM staging system (36) and showed successful results in phase 3 clinical trials (37). For oral carcinoma, identification of immune feature-based prognostic score has been recently introduced by Zhou et al (38) who reported a promising prognostic value for an immunoscore based on the evaluation of CD3 in central areas and at invasive margins of OSCC; CD8, CD45RO, and FOXP3 in the central part of OSCC; FOXP3 and CD45RO at invasive margins of OSCC. However, the proposed immunoscore for OSCC will require further validation.…”