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

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Tumor Biology

Abstract

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.

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Acknowledgments

This work was supported by a grant from the National Natural Science Foundation of China (No. 81402238, 81072213, 81271698), the Nanjing Medical Science & Research Project (No. YKK13145), Nanjing Medical Young engineer (QRX113311), National Key Disciplines Constructional Project Funding (Since 2011), Jiangsu Provincial Clinical Medicine of Science and Technology project (Grant No BL2012017), Nanjing Municipal Key Medical Laboratory Constructional Project Funding (Since 2012), Center of Nanjing Clinical Medicine of tumor project (Since 2014).

Conflict of interest

The authors have no conflict of interest related to this publication.

Authors’ Contributions

YH. N and L.D participated in the design of experimental protocols and drafted the manuscript. L.D. and XF.H. participated in the data collection and immunohistochemical staining and data collection. L.D.,YH.N., and YC.D. performed the statistical analysis and participated in manuscript preparation. QG H and YH N conceived of this idea, outlined study design, and helped manuscript preparation. All authors have read and approved the final manuscript.

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Authors and Affiliations

  1. Central Laboratory of Stomatology, Nanjing Stomatology Hospital and the State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, 210093, China

    Yan-Hong Ni, Liang Ding & Ya-Yi Hou

  2. Department of Oral and Maxillofacial Surgery, Nanjing Stomatology Hospital, Medical school, Nanjing University , 30 Zhong Yang Road, Nanjing, 210008, China

    Xiao-Feng Huang, Ying-chun Dong & Qin-Gang Hu

  3. Medical School, Nanjing University, Nanjing, 210093, China

    Ya-Yi Hou

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  1. Yan-Hong Ni
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  2. Liang Ding
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Correspondence to Qin-Gang Hu or Ya-Yi Hou.

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Ni, YH., Ding, L., Huang, XF. et al. Microlocalization of CD68+ tumor-associated macrophages in tumor stroma correlated with poor clinical outcomes in oral squamous cell carcinoma patients. Tumor Biol. 36, 5291–5298 (2015). https://doi.org/10.1007/s13277-015-3189-5

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  • DOI: https://doi.org/10.1007/s13277-015-3189-5

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