The presence of tumour-infiltrating lymphocytes (TILs) and the ratios between different subsets serve as prognostic factors in advanced hypopharyngeal squamous cell carcinoma.
BACKGROUND
Cancer cells induce the infiltration of various immune cells that are located or distributed in different sites and play multiple roles, which have recently been proposed to predict clinical outcomes. We therefore studied the prognostic significance of the presence of tumour-infiltrating lymphocytes (TILs) and the ratios between different types of immune cells in hypopharyngeal squamous cell carcinoma (HPSCC).


METHODS
We retrospectively analysed 132 consecutive patients diagnosed with advanced HPSCC in 2013-2017. Tumoural parenchyma was immunohistochemically counted manually for the number of CD8, CD4 and Foxp3 cells. The ratios of CD8/Foxp3 and CD8/CD4 ratios were calculated for each specimen and analyzed with respect to patient clinicopathological variables and prognosis.


RESULTS
HPSCC patients with high levels of TILs showed evident correlations with well differentiated tumors (P < 0.05). Moreover, Foxp3+ TIL is also associated with overall staging group and T category (P = 0.048 and P = 0.046, respectively). Kaplan-Meier analysis showed that high CD8 and FoxP3 infiltration correlated with favourable overall survival (OS, P = 0.019 and P = 0.001), disease-free survival (DFS, P = 0.045 and P = 0.028) and distant metastasis-free survival (DMFS, P = 0.034 and P = 0.009), respectively, but only Foxp3 displayed prognostic significance for DMFS in multivariate analysis (MVA). In the lymphocyte ratio analysis, CD8/Foxp3 appeared to play a pivotal role, and patients with a high CD8/Foxp3 ratio had a superior 3-year DFS and DMFS compared with those a low CD8/Foxp3 ratio in both univariate analysis (UVA) and MVA (P = 0.015 and P = 0.011). A high CD8/CD4 ratio was associated with better DFS and local relapse-free survival (LRFS) in UVA, and was an independent prognostic factor for improved LRFS in MVA (P = 0.040).


CONCLUSION
Although high TILs levels were determined to be prognostically significant in advanced HPSCC, the ratios of these subsets may be more informative. Particularly, a higher ratio of CD8/Foxp3 accurately predicts prognosis for improved DFS and DMFS, and an increased CD8/CD4 ratio is an independent predictor for favourable LRFS.
['Wang|Jie|J|', 'Tian|Shu|S|', 'Sun|Ji|J|', 'Zhang|Jiahao|J|', 'Lin|Lan|L|', 'Hu|Chunyan|C|http://orcid.org/0000-0001-7679-5450']
D000328:Adult D000368:Aged D016516:CD4-CD8 Ratio D018414:CD8-Positive T-Lymphocytes D005260:Female D051858:Forkhead Transcription Factors D006801:Humans D007012:Hypopharyngeal Neoplasms D007111:Immunity, Cellular D053208:Kaplan-Meier Estimate D016246:Lymphocytes, Tumor-Infiltrating D008297:Male D008875:Middle Aged D011379:Prognosis D012189:Retrospective Studies D000077195:Squamous Cell Carcinoma of Head and Neck
Tumour-infiltrating lymphocytes Advanced hypopharyngeal squamous cell carcinoma CD8/CD4 ratio CD8/Foxp3 ratio Immunohistochemistry