Microlocalization of CD68⁺ tumor-associated macrophages in tumor stroma correlated with poor clinical outcomes in oral squamous cell carcinoma patients

CD68 has been widely used as a pan-macrophage marker for tumor-associated macrophages (TAM) which always involve in carcinogenesis. But the correlations between CD68⁺ TAMs and prognosis of patients show to be inconsistent, which might due to lack of specific markers of TAMs. We here found that the microlocalization of CD68⁺ TAMs also played a unique role in prognosis of patients with oral squamous cell carcinoma (OSCC). CD68⁺ TAMs were identified in paraffin-embedded OSCC specimens (n = 91) by using immunohistochemistry. The number of CD68⁺ TAMs was remarkably increased from adjacent none-neoplasia tissues (NT) to tumor nest (TN), but tumor stroma (TS) was infiltrated with highest frequency of CD68⁺ TAMs (P < 0.0001). Unexpectedly, more CD68⁺ TAMs in TS, but not NT or TN, were associated with high tumor grade (P = 0.033), lymph node metastasis (P = 0.034), and shorter 10-year overall survival time, disease free survival. Considering TAMs was derived from monocytes in peripheral blood, we assessed the relationship between leukocytes in peripheral blood and CD68⁺ TAMs in OSCC and found that more CD68⁺ TAMs in TS were accompanied with decreased monocytes and lymphocytes in peripheral blood (P < 0.05). Although Cox regression analysis revealed that CD68⁺ TAMs in TS were not an independent prognostic factor for OSCC patients, we raised a possibility that the microlocalization of CD68⁺ TAMs was an indispensable factor for the advance of OSCC.