Density of CD3+ and CD8+ cells in gingivo-buccal oral squamous cell carcinoma is associated with lymph node metastases and survival

Abstract

The tumor immune microenvironment is emerging as a critical player in predicting cancer prognosis and response to therapies. However, the prognostic value of tumor-infiltrating immune cells in Gingivo-Buccal Oral Squamous Cell Carcinoma (GBOSCC) and their association with tumor size or lymph node metastases status require further elucidation. To study the relationship of tumor-infiltrating immune cells with tumor size (T stage) and lymph node metastases (N stages), we analyzed the density of tumor-infiltrating immune cells in archived, whole tumor resections from 94 patients. We characterized these sections by immune-histochemistry using 12 markers and enumerated tumor-infiltrating immune cells at the invasive margins (IM) and centers of tumors (CT). We observed that a higher density of CD3+ cells in the IM and CT was associated with smaller tumor size (T1-T2 stage). Fewer CD3+ cells was associated with larger tumor size (T3-T4 stage). High infiltration of CD3+and CD8+ cells in IM and CT as well as high CD4+ cell infiltrates in the IM was significantly associated with the absence of lymph node metastases. High infiltrates of CD3+ and CD8+ cells in CT was associated with significantly improved survival. Our results illustrate that the densities and spatial distribution of CD3+ and CD8+ cell infiltrates in primary GBOSCC tumors is predictive of disease progression and survival. Based on our findings, we recommend incorporating immune cell quantification in the TNM classification and routine histopathology reporting of GBOSCC. Immune cell quantification in CT and IM may help predict the efficacy of future therapies.

Prognostic Role of Combined EGFR and Tumor-Infiltrating Lymphocytes in Oral Squamous Cell Carcinoma

“…The sole explanation for the favorable OS observed in EGFR+/CD3+ patients was the significant association with decreased lymph node metastasis (Table 2). This finding is quite contradictory since increased EGFR is associated with increased lymph node metastasis (70) but increased CD3 expression has been associated with decreased lymph node metastasis (38). It is unclear how the presence of CD3+ T cells overrides the tumor promoting effects of EGFR.…”

“…Recently, growing evidence for the interaction of tumor and immune cells in tumor growth, recurrence and progression has emerged (37)(38)(39)(40)(41). OSCCs due to its unique anatomical location are characterized by an abundant infiltrate of immune cells (42).…”

“…Cells that contribute to immune escape mechanisms include tumor-associated macrophages (45), regulatory dendritic cells (DCs) (46), T regulatory cells (Tregs) (47) and myeloid-derived suppressor cells (MDSCs) (48,49). On the other hand, in many cancers including OSCCs, an active anti-tumor immune response is often reflected by the abundance of tumor-infiltrating lymphocytes (TILs) such as CD8+ T cells (41,50,51) and is correlated with favorable prognosis (37)(38)(39)(40). Tumor-infiltrating CD4+ T cells have recently been correlated with favorable prognosis in OSCCs (52) however CD4+ T cells consist of several subpopulations (including Tregs) and CD4 expression as a prognostic biomarker in OSCCs and HNSCCs is controversial (40,(53)(54)(55).…”

The bioinformatics and experimental analysis of AlkB family for prognosis and immune cell infiltration in hepatocellular carcinoma

“…Then, previous studies showed that immune cell infiltration plays a crucial role in tumorigenesis, prognosis and therapies ( Mukherjee et al, 2020 ; Xu et al, 2020c ; Yan et al, 2020 ). Most T cells and macrophage-mediated phagocytosis are capable of killing tumor cells and preventing tumor growth ( Feng et al, 2019 ).…”

Development and therapeutic manipulation of the head and neck cancer tumor environment to improve clinical outcomes

“…A good example of the impact of immune cells on treatment outcome is that HNSCC patients with increased immune infiltrate, particularly of T cells, have improved overall and cancer free survival. This includes oral squamous cell carcinoma (OSCC) which is typically HPV negative (HPV-) and induced by carcinogen exposure (such as alcohol and cigarette exposure) [2,3]. In 119 patients with HPV-OSCC, increased infiltrations of CD8 T cells at the invasive margin (IM) was associated with increased overall survival following treatment [2].…”