Increased malignancy of oral squamous cell carcinomas (oscc) is associated with macrophage polarization in regional lymph nodes – an immunohistochemical study

Abstract

BackgroundIt is largely accepted that specific immunological parameters in solid malignancies are associated with patient’s prognosis. Recently a correlation of macrophage polarization with histomorphological parameters could also be shown in oral squamous cell carcinoma (oscc). The observed tumor derived peripheral immune tolerance could be associated with the macrophage polarization in regional tumor draining lymph nodes.So far there are no studies analyzing the macrophage polarization in cervical lymph nodes of oscc patients. In the present study we aimed to correlate macrophage polarization in different anatomical lymph node compartments of patients diagnosed with oscc with histopathologic parameters of the primary tumor (T-, N-, L-, V-, Pn-status, grading).MethodsTumor free (n = 37) and metastatic (n = 17) lymph nodes of T1 and T2 oscc patients were processed for immunohistochemistry to detect CD68, CD11c, CD163 and MRC1 positive cells. Samples were digitized using whole slide imaging and the number of cells expressing the aforementioned markers in the region of interest quantitatively analyzed.ResultsThe malignancy of the primary tumor (defined by T-, L-, Pn-status, grading) correlated with the lymph node macrophage polarization. L1 and Pn1 tumor cases displayed a significantly (p < 0.05) decreased M1 and increased M2 polarization in the sinus of the lymph nodes. G3 cases presented a significantly (p < 0.05) increased M2 polarization in the sinus compared to G2 cases. T2 tumors had significantly (p < 0.05) increased M2 polarization in the interfollicular zone of regional lymph nodes compared to T1 tumors. Metastatic and non-metastatic lymph nodes did not differ regarding their macrophage polarization.ConclusionsThe current study revealed for the first time an influence of oscc on the macrophage polarization in regional lymph nodes. Markers of malignant behavior in the primary tumor were associated with a shift of macrophage polarization in lymph nodes from the anti-tumoral M1 type to the tumor-promoting M2 type. As tumor free and metastatic lymph nodes did not differ in terms of their macrophage polarization pattern, there must be other factors influencing the location for lymph node metastasis formation.

Role of tumour-associated macrophages in oral squamous cells carcinoma progression: an update on current knowledge

“…There is compelling evidence that tumour-associated macrophages (TAMs) have potential involvement in the progression and metastatic spread of OSCC. The most important features associated with their presence in the lesion stroma include facilitation of angiogenesis, tumour cell invasion, augmentation of cell motility, persistent growth, and suppression of anti-tumour responses [9–13]. The signals involved in communication between tumour cells and macrophages have not yet been completely elucidated.…”

Modulation of inflammation by low and high doses of ionizing radiation: Implications for benign and malign diseases

“…For example, soluble CD163 and the presence of CD68 + TAMs at the invasive front of the tumor were independent prognostic factors for overall survival of patients with stage I/II melanoma before definitive surgery [36]. Further, Wehrhan and colleagues revealed that an increased malignancy of oral squamous cell carcinomas is associated with polarization of macrophages to the M2 type in regional lymph nodes [78]. Altogether, these data suggest TAMs as potential biomarkers with prognostic/ predictive relevance and may support the development of novel agents targeting TAMs in combination with RT/RCT.…”

Determining the potential of desmoglein 3 as a sensitive and specific immunohistochemical marker for the detection of micrometastasis in patients with primary oral squamous cell carcinoma

“…Oberg et al . (2002) showed that poor patient survival correlates with the number of M2 macrophages [22]. …”

“…This tumour antigen is then engulfed and concentrated within the TAMs [25]. Direct communication between macrophages and tumour cells is said to prepare the regional lymph nodes for the acceptance and sustenance of metastases [22, 26]. …”