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.
Highlights
Chewing tobacco is a habit very prevalent in India
One study showed that patients with leukoplakia without malignant transformation had higher numbers of CD3+ cells than patients whose leukoplakia transformed to oral squamous cell carcinoma [46]
Granzyme B+ cells were found to be significantly higher in invasive margin (IM) and center of tumor (CT) of T1-T2 stage tumors compared to T3-T4 tumors suggesting that small tumor size may be attributed to Granzyme B mediated killing of tumor cells [50]
Summary
Chewing tobacco is a habit very prevalent in India. It is the strongest risk factor for the development of oral cancer. Oral cancer comprises about 12% of all male cancers in India, of which about 40% are gingivobuccal [1, 2].The incidence of Oral Squamous Cell Carcinoma of the Gingivo-Buccal region (GBOSCC) includes buccal mucosa, gingivo-buccal sulcus, alveolus and retro-molar trigone. India has one of the highest incidences of this form of cancer in the world. Despite advances made in treatment modalities, locoregional recurrence is the primary cause of treatment failure in advanced stages of the disease [3] with a dismal 5-year survival rate between 5–15% [4]. Nodal metastases is the most significant adverse prognostic factor of GBOSCC survival [5]
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