Cancer Management and Research (Sep 2020)
Digital Image Analysis of CD8+ and CD3+ Tumor-Infiltrating Lymphocytes in Tongue Squamous Cell Carcinoma
Abstract
Yenlin Huang,1,2 Chieh Lin,3 Huang-Kai Kao,2,4 Shao-Yu Hung,4 Hung-Ju Ko,2 Yu-Chen Huang,5 Yu-Liang Chang,5 Kai-Ping Chang2,6 1Department of Anatomic Pathology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 2College of Medicine, Chang Gung University, Taoyuan, Taiwan; 3Department of Nuclear Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 4Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 5Department of Oral & Maxillofacial Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 6Department of Otolaryngology - Head & Neck Surgery, Chang Gung Memorial Hospital, Taoyuan, TaiwanCorrespondence: Kai-Ping ChangDepartment of Otolaryngology - Head & Neck Surgery, Chang Gung Memorial Hospital, No. 5, Fu-Hsing Street, Kwei-Shan, Taoyuan 333005, TaiwanTel +886-3-3281200 ext 3972Fax +886-3-3979361Email [email protected]: The presence of CD8+ tumor-infiltrating lymphocytes (TILs) has been reported to be associated with treatment outcomes in many types of solid tumors. However, the results vary due to the various methods of visual estimation and subjective interpretation. The current study is the first to use digital image analyses to evaluate the density of CD8+/CD3+ TILs in tongue squamous cell carcinoma (TSCC).Patients and Methods: From 2005 to 2015, a cohort of 258 TSCC patients were consecutively enrolled in this study. After immunohistochemistry on representative sections, the density of CD8+/CD3+ TILs at tumor invasive margins was evaluated by digital image analysis. The subjects were stratified by the median values of CD3+ cell density, CD8+ cell density, CD8/CD3, and scores (0, 1, and 2) to demonstrate the association with various clinicopathological manifestations.Results: Low CD8+ TIL counts were associated with advanced tumor stages (p=0.034), and low CD8/CD3 ratios were associated with perineural invasion (p=0.043). Both parameters were also associated with increased tumor depths (p=0.034 and 0.004, respectively). Univariate analyses revealed that advanced tumor stages, perineural invasion, extranodal extension, tumor depth, lower CD8 counts, and lower scores (score 0 vs 2) were associated with poorer overall survival, and multivariate analysis further indicated that extranodal extension and low scores (score 0 vs 2) were both independent factors for overall survival (p < 0.0001 and p = 0.0369, respectively).Conclusion: The use of digital image analysis to assess CD8+ TILs at the invasive margins provides an objective indicator of prognoses including overall survival.Keywords: oral cavity, squamous cell carcinoma, oral cancer, SCC, tumor-infiltrating lymphocyte, TIL
