| Autor: |
T. Hulett, Tuan Bui, C. Dubay, C. Paustian, Carlo Bifulco, Hong-Ming Hu, Zipei Feng, Bernard A. Fox, Rom Leidner, A. Cheng, T. Hilton, T. Moudgil, Richard Bryan Bell |
| Rok vydání: |
2014 |
| Předmět: |
|
| Zdroj: |
Journal of Oral and Maxillofacial Surgery. 72:e1 |
| ISSN: |
0278-2391 |
| DOI: |
10.1016/j.joms.2014.06.004 |
| Popis: |
wer than TNM staging in patients with colon cancer. 1,2 Similar to observations in other malignancies, CD8 effector T cell infiltration or transcriptional signature consistent with an ongoing T cell response is associated with prolonged survival in patients with oral, head and neck squamous cell carcinoma (OHNSCC). This suggests that OHNSCC lacking a T cell infiltrate may benefit from immune interventions that induce and/or augment a tumor-specific immune response. To develop a strategy to address this problem we have created an OHNSCC tumor bank that is cryopreserving enzymatically isolated viable cells from resected tumors. Furthermore, we are attempting to develop primary tumor cell lines and are isolating tumor-infiltrating lymphocytes from theses specimens.The purpose of this preliminary investigation was to apply digital imaging and objective assessment techniques to characterize infiltrating immune cells and to coordinate these data with a flow cytometric analysis of the cells isolated from the tumor and evaluate for possible correlation with tumorspecific function. Materials and Methods: 102 subjects with biopsy proven OHNSCC from a variety of subsites underwent surgery with curative intent and were enrolled into this prospective, IRB approved trial. Samples of tumor were obtained from either the primary tumor or from a metastatic lymph node and processed utilizing mechanical and enzymatic digestion to dissociate cell types contained in the tumor specimen. These cells are being analyzed for CD3, CD4, CD8, CD20 and FoxP3 using flow cytometry. In parallel, formalin fixed parafin embedded (FFPE) tissue from the same specimens are being stained for the specified markers, scanned and digital images are being assessed using the Definiens software platform. Methods of Data Analysis: Descriptive statistics. Results: Preliminary results have documented consistent staining and potential of the IHC and FACS-based systems to identify infiltrating cells. Definiens software provides a consistent method to assess numbers of IHC stained cells in sections of tumor specimens. Ten confirmed tumor cell lines are established thus far and T cells from 9 of 11 TIL cultures tested to-date secreted IFN-g when stimulated with their autologous tumor cells. Conclusion: While still early, both methodologies can provideinsightsintothetype,number,function,specificity or relative location of immune cells present in the tumor microenvironment. Planned studies will assess these markers using IHC in larger cohorts of patients with longterm follow-up. While we anticipate that a strong infiltrationofimmunecells(immunoscorepositive)willbeassociated with better clinical outcomes, the value of the current study will be the availability of isolated and cryopreserved tumor and tumor-infiltrating immune cells for functional studies. Assessment of the tumor cells from immunoscore negativetumorsmayprovideinsightsintothemechanisms responsible for the absence of infiltrating immune cells. Theseinsightsmaybeexploitedtodevelopnoveltherapeutic strategies that will reverse the negative immunoscore and improve outcomes of patients with OHNSCC. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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