Prognostic Potential of Tumor-Infiltrating Immune Cells in Resectable Oral Squamous Cell Carcinoma

SIMPLE SUMMARY: Oral cancer is a common malignancy with high morbidity and mortality. Tumor-infiltrating immune cells play key roles in its pathogenesis, influencing tumor behavior and evolution. The aim of our study was to assess the prognostic character of tumor-infiltrating CD4(+), CD8(+) and CD56(+) cells in oral squamous cell carcinoma. We found major differences in CD4(+) and CD8(+) lymphocyte density at the front of invasion compared to the intratumor compartment. In addition, intense infiltration with CD8(+) lymphocytes in both compartments carried a positive prognostic character. Moreover, we found that a higher intratumor infiltration with CD56(+) cells significantly correlated with locoregional disease control and improved survival. Our study confirms the key role of innate and adaptive immune systems in oral squamous cell carcinoma. The predictive characteristics of CD8(+) and CD56(+) cells can be implemented as independent prognostic tools and can provide important elements in developing individualized therapy in the fight against oral cancer. ABSTRACT: (1) Background: The immune microenvironment plays an important role in carcinogenesis and has prognostic potential in many types of cancer. In this study we assess the prognostic character of tumor-infiltrating immune cells CD4(+), CD8(+) and CD56(+) in resectable oral squamous cell carcinoma (OSCC); (2) Methods: We have evaluated the densities of CD4(+), CD8(+) and CD56(+) in two distinct compartments, intratumor and invasion front, in 90 patients with OSCC; (3) Results: Significant differences were found between the tumor compartments for the CD4(+) and CD8(+) lymphocytes. An improved outcome (OS) was seen in patients with high densities of intratumor CD8(+) lymphocytes (p = 0.0086), CD8(+) lymphocytes at the front of invasion (p = 0.0011) and for intratumor CD56(+) cells (p = 0.0016). Multivariate analysis confirmed the independent prognostic role of CD8(+) at the front of invasion (OR = 3.75, CI95% 1.17–12.35, p = 0.026) and for intratumor CD56(+) cells (OR = 3.669, CI95% 1.09–15.37, p = 0.035); (4) Conclusions: Tumor-infiltrating CD8(+) lymphocytes at the front of invasion and CD56(+) in the intratumor compartment display predictive traits in OSCC. A reach immune infiltration with these types of cells is associated with an improved patient outcome.