Lymphocytic Host Response to Oral Squamous Cell Carcinoma: An Adaptive T-Cell Response at the Tumor Interface

Abstract

Lymphocytic host response (LHR) in the RiskModel is histologically quantified as the density of lymphocytes at the tumor interface (Brandwein-Gensler in Am J Surg Pathol, 34:676-688, 1; in, Am J Surg Pathol 29:167-178, 2). It is classified as strong, intermediate or weak, and is inversely associated with the risk of decreased time to disease progression. In this study, we test the hypothesis that strong LHR corresponds to a greater degree of adaptive cytotoxic T cell response as compared to moderate LHR. We studied resection specimens of primary oral squamous carcinoma classified as having either strong (n = 16), intermediate (n = 20) or weak (n = 4) LHR. CD20?, CD4?, & CD8? cells were detected by immunohistochemistry and quantified at 409 with a grid; counting the 10 fields with the most lymphocytes at the tumor interface and within tumors. Mean counts/tumor were analyzed by the 2-sided T-test. Statistically significant differences were observed for interface CD8 cells with respect to strong versus moderate LHR, strong versus weak LHR, and moderate versus weak LHR, and tumor infiltrating CD8 cells with respect to strong versus weak LHR. Statistically significant differences were also observed for interface CD4 cells with respect to strong versus weak LHR, and moderate versus weak LHR. Statistically significant differences in interface B cell counts were seen with respect to strong versus weak LHR, and moderate versus weak LHR. Decreased CD8? T cells were significantly associated with higher stage at presentation (P = 0.005); a direct, but nonsignificant correlation was seen between decreased CD8? T cells and decreased survival time.Immune response at the tumor interface correlates with an adaptive T cell response; the degree of cytotoxic CD8? cells infiltrate can distinguish between strong and intermediate LHR at the interface of oral carcinomas.

Validation of the Risk Model: High-Risk Classification and Tumor Pattern of Invasion Predict Outcome for Patients with Low-Stage Oral Cavity Squamous Cell Carcinoma

“…LHR assessment presently does not require quantification of specific lymphocyte populations, however we have previously demonstrated that T cells are the predominant lymphocyte at the tumor advancing edge [23]. Figure 4a demonstrates a carcinoma with strong LHR throughout the advancing tumor interface.…”

Tumor immune microenvironment in head and neck cancers

“…In addition to dysfunctional T cells, decreased expression of major histocompatibility complexes (MHC), called HLA in humans, may also help the tumor cells evade adaptive immunity. MHC class I is essential for presenting peptides to CD8 + T cells and for CD8 + cytotoxic T lymphocytes (CTL) to recognize tumor cells expressing tumor‐associated or tumor‐specific antigens 50 . About 50% of HNSCC tumors might evade immune surveillance through the downregulation of MHC class I molecules 38 .…”

The protective effect of p16INK4a in oral cavity carcinomas: p16Ink4A dampens tumor invasion—integrated analysis of expression and kinomics pathways

“…35,51,52 Enhanced local adaptive immunity is known to have a protective impact on outcome in oral cavity squamous cell carcinoma and directly associates with cytotoxic CD8 cells. 3,4,53 Here we show that HPV16/18 in oral cavity squamous cell carcinoma is not associated with enhanced local adaptive immunity. In contrast, we and others have demonstrated enhanced local immune response in HPV-mediated oropharyngeal squamous cell carcinoma.…”