Distribution Of Immune Populations In Patients With Oral Squamous Cell Carcinoma

Presentation: S072
Topic: Skin Cancers
Type: Oral
Date: Sunday, July 17, 2016
Session: 1:45 PM - 3:15 PM Immunotherapy
Authors: Zipei Feng1, Daniel Bethmann, MD2, Matthias Kappler, MD3, Carmen Ballesteros-Merino, PhD4, Alexander Eckert, MD3, R. Bryan Bell, MD, DDS5, Allen Cheng, MD, DDS5, Tuan Bui, MD, DMD5, Rom Leidner, MD4, Carlo Bifulco, MD4, Claudia Wickenhauser, MD2, Barbara Seliger, PhD6, Bernard Fox, PhD4
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Institution(s): 1Oregon Health & Science University, Department of Cell, Development & Cancer Biology, 2Martin Luther University Halle-Wittenberg, Institute of Pathology, Halle, Germany, 3Martin Luther University Halle-Wittenberg, Department of Oral and Maxillofacial Plastic Surgery, 4Robert W. Franz Cancer Research Center, Earle A. Chiles Research Institute, Providence Cancer Center, Portland, OR, 5Oral, Head and Neck Cancer Program and Clinic, Providence Cancer Center, Portland, OR, 6Martin Luther University Halle-Wittenberg, Institute of Medical Immunology
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Background: Assessment of distribution of immune cells in the tumor using immunohistochemistry (IHC) is a powerful tool to predict patients’ prognosis in various types of cancers [1, 2]. Oral squamous cell carcinoma (OSCC) is no exception; various reports have demonstrated that T cell infiltration is associated with prolonged survival [3, 4]. Many of the studies are performed in HPV-positive oropharyngeal population. However, the role of immune impact is less clear in the HPV-negative setting. Multiplex imaging and relationship analysis have emerged as powerful techniques to objectively study the various immune interactions taken place in the tumor and how these interactions may have an impact on the overall anti-tumor immune responses. We hypothesize that data from such analyses may be used to direct immunotherapy treatment strategies.

Purpose: To apply multiplex IHC to identify immune biomarkers that correlate with prognosis and further explore relationship analysis to provide insights into immune tolerance mechanisms of tumors.

Materials and methods: Samples from 162 patients with HPV-negative OSCC are included in this study. Slides were prepared from formalin fixed paraffin embedded (FFPE) samples of patients’ primary tumor and stained for CD3, CD8, FoxP3, CD163, PD-L1, cytokeratin and DAPI using the PerkinElmer Opal system. Digital imaging and analysis were performed using PerkinElmer Vectra and inform software.

Resuls: Preliminary data from our discovery cohort indicate a brisker immune infiltrate at the invasive margin compared to the center of the tumor (p<0.0001). At the invasive margin, the number of total CD3+CD8- T cell is positively associated with survival (P<0.01). Intratumoral CD8+ and FoxP3+ cells are positively associated with survival (p<0.05), as well as the ratio of CD8+ to FoxP3+ cells within 30 microns of CD8+ cells (p<0.05). Relationship analysis demonstrates that FoxP3+ T regs are more closely associated with CD163+ macrophages expressing PD-L1 (p<0.01).

Conclusion: Preliminary conclusions from our discovery cohort suggest that interactions between effectors and suppressors may affect survival in HPV-negative OSCC. Interestingly, the expression of FoxP3+ T regs did not negatively impact patients’ prognosis.

Mr. Feng and Dr. Bethmann; and Drs. Seliger and Fox contributed equally to this work.  Supported by the Harder Family, Lynn and Jack Loacker, Robert W. Franz, Wes and Nancy Lematta, the Providence Medical Foundation and the Oral & Maxillofacial Surgery Foundation (RBB, CBB, BAF). 

References: 1. Pages F, et al. NEJM 2005; 2. Galon J, et al. Science 2006; 3. Balermpas, P., et al., Oncoimmunology, 2014; 4. Pretscher, D., et al. BMC Cancer, 2009.