T regulatory cell markers in oral squamous cell carcinoma: Relationship with survival and tumor aggressiveness

Abstract

Abstract. Tumor-infiltrating lymphocytes (TILs) are a heterogeneous cell family which plays an important role in tumorassociated immune response. Of these, T regulatory (Treg) cells have also been shown to inhibit anti-tumor response. We aimed to evaluate the expression of T regulatory cell markers (CD4, CD25, CTLA-4 and FoxP3) in samples of oral cavity squamous cell carcinoma (OCSCC) and lip SCC (LSCC) by immunohistochemistry. The relationship of Treg markers with survival data and the proliferative index were also evaluated. We observed similar numbers of CD4-, CD25-and FoxP3+ cells in OCSCC and LSCC. On the other hand, numbers of CTLA-4 + cells were significantly lower in OCSCC than in LSCC. OCSCC samples with high numbers of CD4 exhibited a high proliferative index, while samples with high CTLA-4 counts demonstrated a low tumoral proliferative index. A log-rank test showed that patients with OCSCC that presented high counts of CD4 showed a significantly decreased survival compared with patients with low cell counts. In contrast, high CD25 + cell counts were associated with increased survival. Our results suggest an association of CD4 with poor prognosis, while CD25 expression is related with favorable prognosis. These findings result from the heterogeneity of TIL subsets that display an antagonistic role in tumor immune cell response.

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

“…Taken together with previous studies investigating Treg cells in these tumors, 16,17 these findings corroborate the presence of this T cell subpopulation in the microenvironment of LLSCC. In the present study, 14 On the other hand, Gaur et al 12 observed a larger number of Treg cells in the peripheral blood of patients with oral SCC who had regional lymph node metastases and were in advanced clinical stages.…”

“…16,17 One of these studies included a relatively small sample of LLSCCs (n = 6) 17 and the other one did not associate the number of these cells with clinical and pathological findings. 16 Thus, the role of Treg cells in the progression of LLSCC remains poorly understood.…”

“…14,15 Studies investigating Treg cells in LLSCC are sparse 16,17 and do not permit categorically establishing the role of this T cell subpopulation in the progression of this cancer.…”

TILs in Head and Neck Cancer: Ready for Clinical Implementation and Why (Not)?

“…The same finding was true for SCCHN as high levels of tumor infiltrating CD4 + CD69 + T cells in these patients were positively correlated with OS and locoregional control [32]. In contrast, others have described CD4 to be a predictor of poor outcome, especially in oral cavity tumors [39]. These contradictory results could be explained by the heterogeneity of the CD4 + T cell population as besides the classical T helper 1 and T helper 2 cells, other subsets have been identified; including T helper 17, follicular helper T cell, T helper 9, and T regs ; each with its proper characteristic cytokine profile [40].…”

Clinical relevance of immune parameters in the tumor microenvironment of head and neck cancers

“…Higher CD8+/T‐regs ratios seem to have a prognostic benefit, which, in turn, suggests that T‐regs may be detrimental within the tumor microenvironment in oral SCC. A further study of T‐regs in oral cavity SCC investigated the relationship between CD4, CD25, CTLA‐4, and FoxP3 staining and survival . In this study, low CD4+ counts and high CD25+ counts were associated with better OS, but there was no correlation with the other parameters, although the study had a relatively small cohort size ( n = 18).…”