Evaluation of Tumor-Infiltrating Lymphocytes as a Prognostic Indicator of Head-and-Neck Squamous Cell Carcinomas

Introduction: The incidence of Head-and-Neck Squamous Cell Carcinomas (HNSCC) is on the rise in our country and worldwide, with a worsening prognosis. The abundance of tumor-infiltrating lymphocytes (TILs) is evolving to be a novel prognostic indicator in assessing treatment response of HNSCC. TILs mainly comprise T lymphocytes, which migrate from blood into the tumor as part of the body's immune response. In this context, targeting the tumor microenvironment with the help of immunotherapy may present a potential approach for better cure of head-and-neck cancers. In the present study, we evaluated the potential TILs parameters which can be used in clinical practice to predict treatment outcomes in HNSCC. Materials and Methods: This is a prospective observational study of 41 patients conducted at a tertiary cancer center between September 2019 and September 2020. All patients with biopsy proven, primary/recurrent HNSCC, without distant metastasis, and complete clinicopathological data were included in the study. Patients with a nonsquamous cell carcinoma, patients who underwent upfront chemotherapy or chemoradiotherapy were excluded from the study. Patients who had follow-up of <1 year or lost to follow-up were excluded from the study. Parameters analyzed include mean age; percentage of cluster of differentiation 3 (CD3) cells; CD4, CD8, and FOXP3cell counts; distribution of CD57 and CD3/FOXP3 ratio. Results: A total number of 19 patients were grouped under the nonrecurrence TILs and 22 patients under recurrent TILs category. Majority of the patients (90.2%) had oral cavity squamous cell carcinoma. 68.42% of nonrecurrent cases and 36.36% of recurrent cases were found to be harboring Hot tumors. Using odds ratio, it was noted that the odds of having Hot tumor is 3.79 times (95% confidence interval: [1.03,13.91]) higher in nonrecurrent TILs than in recurrent TILs group. CD3 cell count was higher in nonrecurrent cases (54.74 ± 18.37) than in recurrent cases (42.73 ± 16.09) with P = 0.0157. Using two tailed t-test, it was noted that the mean of CD4, CD8, and FOXP3 is not significantly different between nonrecurrent and recurrent tumor TILs groups. Conclusion: To summarize, we have shown that the CD3/FOXP3 cell ratio, rather than the individual proportion of TILs, is a significant prognostic indicator in HNSCC. It's also been shown that people with Cold tumors have a higher risk of recurrence than those with Hot tumors. Our findings confirm the importance of host immunity in prognosis and suggest that the degree of immune cell infiltration in the tumor microenvironment is a major independent prognostic factor that merits further investigation as a potentially valuable biomarker in HNSCC patients.