Tumor infiltrating lymphocytes (TIL) and prognosis in oral cavity squamous carcinoma: A preliminary study

Abstract

Objectives Tumor infiltrating lymphocytes (TILs) in the microenvironment reflect may tumor biology and predict outcome. We previously demonstrated that infiltrates of CD4, CD8, and FoxP3 positive lymphocytes were associated with HPV-status and survival in oropharyngeal cancers. To determine if TILs were of prognostic importance in oral cancer, TIL levels were evaluated retrospectively in 52 oral cancer patients treated with surgery and correlations with outcome determined. Methods Complete TIL and clinical data were available for 39 patients. Levels of CD4, CD8, FoxP3 (Treg), CD68 and NK cells were assessed by immunohistochemistry in tumor cores on a tissue microarray. Associations with clinical variables, tobacco and alcohol use and histologic features were assessed using Spearman correlation coefficient and the non-parametric Kruskal-Wallis testing. Timeto-event outcomes were determined using univariate and multivariate Cox models. Median follow up was 60 months. Results The ratio of CD4/CD8 (p=.01) and CD8 infiltrates (p=.05) were associated with tumor recurrence but not overall survival. Lower CD4 infiltrates were associated with alcohol use (p=.005) and poor tumor differentiation (p=.02). Interestingly, there higher levels of CD68+ macrophages were found associated with positive nodes (p=.06) and poorer overall survival (p=.07). Overall and DSS survival were significantly shorter for patients with positive nodes, extracapsular spread , or perineural invasion. Conclusions Infiltrating immune cell levels in oral cavity cancer appear influenced by health behaviors and tumor characteristics. In contrast to oropharynx cancer, infiltrates of CD68 positive tumor associated macrophages may contribute to metastatic behavior and outcome in advanced oral cavity carcinoma.

CD70 Expression and Its Correlation with Clinicopathological Variables in Squamous Cell Carcinoma of the Head and Neck

“…In agreement with previous reports [14,15], we found that SCCHN patients with tumors densely infiltrated by TILs had a prolonged OS compared to patients with poorly infiltrated tumors. Also, a trend towards less TIL infiltration in SCCHN with higher CD70-expression was observed.…”

T-helper and T-regulatory cells modulation in head and neck squamous cell carcinoma

“…Some reports have shown a decrease of tumor-infiltrating lymphocytes (TIL) in HNSCC, 9 but the clinical outcome seems to depend more on the type of TIL rather than on their total number. For instance, cytotoxic CD8 C T cells are significantly decreased in HNSCC patients if compared with healthy controls, [9][10][11][12][13][14][15] probably due to an increase apoptotic rate among this cell population in HNSCC. 13 On the top of that T cells isolated from HNSCC patients are significantly less responsive to in vitro stimulation than those isolated from healthy controls.…”

Immunohistochemical analysis of FoxP3+ regulatory T cells in lower lip squamous cell carcinomas

“…In this respect, depending on the profile of immune cells and secreted chemical mediators, the tumor-associated inflammatory infiltrate can exert an antitumor or protumor effect. 13,15 Therefore, research into the cellular and molecular features of the immune response to tumors has intensified in recent years in an attempt to obtain a better understanding of the process of tumor progression, to identify more reliable prognostic factors, and to eventually define potential targets for immunotherapeutic strategies. 6,13,22,23 Within the context of immune responses to tumors, studies have highlighted the participation of Treg cells, which can suppress the functions of different immune system cells.…”

“…8 By contrast, other studies showed that larger numbers of Treg cells, both in the peripheral blood of patients 14 and in the tumor environment, 15 are associated with a better prognosis of oral SCCs. Similarly, studies on gastric adenocarcinomas 25 and head and neck carcinomas 7,26 demonstrated a relationship between a larger number of Treg cells in the tumor microenvironment and higher patient survival rates.…”