Elsevier

Oral Oncology

Volume 48, Issue 7, July 2012, Pages 594-601
Oral Oncology

Radiochemotherapy induces a favourable tumour infiltrating inflammatory cell profile in head and neck cancer

https://doi.org/10.1016/j.oraloncology.2012.01.024Get rights and content

Summary

Head and neck squamous cell cancers (HNSSC) generate an immune-suppressive micro-environment by a specific pattern of tumour infiltrating inflammatory cells. The aim of our study was to evaluate the impact of radiochemotherapy on the numbers and composition of inflammatory cells and its influence on outcome.

Fifty-eight patients suffering from oral cavity cancer were studied, whose therapy consisted of concurrent radiochemotherapy followed by surgery. Numbers and ratios of tumour infiltrating inflammatory cells were compared prior to and after radiochemotherapy. Intraepithelial and stromal location of tumour infiltrating inflammatory cells was analysed separately.

Infiltration of CD3+, CD4+, CD25+, FoxP3+, CD8+, Granzyme B+, CD20+ and CD68+ cells predominated in the peritumoural stromal compartment, whereas CD1a+ dendritic cells were found more frequently in the intraepithelial compartment. Neoadjuvant treatment was associated with a general decrease of tumour infiltrating inflammatory cells in both compartments. The CD8+ and Granzyme B+ cytotoxic cells decreased only slightly after RCT. In contrast, the decrease of FoxP3+ regulatory T cells was more pronounced and the cytotoxic T-cell/FoxP3+ ratio increased 2- to 3-fold in both compartments, respectively. Patients with high cytotoxic cell numbers, high dendritic cell numbers and a high ratio of cytotoxic cells to regulatory T cells had a better disease free survival.

Concurrent radiochemotherapy of oral squamous cell carcinoma was shown to drive the composition of inflammatory cells in a direction which is supposed to be prognostically favourable.

Introduction

There is sufficient evidence that immune cells play a critical role in the control of malignancy.1, 2 Moreover, it is evident that cancers can suppress the host immune system. Especially HNSCC corrupt the immune system by a variety of mechanisms.3, 4 For cancer cure the presence of functional intact tumour infiltrating inflammatory cells seems to be favourable. Generally the tumour infiltrating inflammatory cells (TIC) are putative prognostic factors. Many studies on TIC in HNSCC have evaluated the effect of immune cell subsets on prognosis.5 Brandwein-Gensler et al. found that a weak or limited lymphocyte infiltration in over 200 squamous cell carcinomas at the tumour and stromal margin was associated with increased locoregional recurrence and decreased overall-survival.6 Intratumoural accumulation of CD4+CD25+FoxP3+ regulatory T cells (Treg) was associated with worsened survival rates of HNSCC patients, especially in advanced stages.7 Suwa et al. found that the proliferative activity of CD8+ TIC at the tumour site was enhanced by preoperative radiotherapy in HNSCC.8

However, the influence of radiotherapy (RT) or radiochemotherapy (RCT) on the TIC infiltration and composition in situ has to our knowledge not been investigated in patients suffering from HNSCC. It is important for the development of immunotherapeutic strategies to understand the local immune response in head and neck cancers after radiochemotherapy.9 Therefore, the aim of this study was to evaluate the morphological distribution of tumour infiltrating inflammatory cells prior to and after radiochemotherapy and their impact on patients’ prognosis. Fifty-eight patients with squamous cell carcinoma of the oral cavity were treated by neoadjuvant simultaneous RCT followed by curative surgery. We used pretherapeutic diagnostic biopsies and compared them to the postRCT resected tissue. The relationship between the cell populations in stromal and intratumoural compartments pre and postRCT and their prognostic values were investigated.

Section snippets

Patient selection

Between 1997 and 2005, a total of 58 patients with histologically proven advanced squamous cell carcinoma of the oral cavity were treated at this University Hospital by neoadjuvant concurrent RCT followed by curative surgery. All 58 patients (Table 1) were included in this study according to the following criteria: squamous cell carcinoma of the oral cavity; age between 18 and 75 years; sufficient haematological, liver and renal function; absence of distant metastases and second cancer. Staging

Clinical results

Clinical characteristics of the study group are given in Table 1. Overall- and NED-survival rates of all patients were 55% and 36% at 8 years, respectively (Fig. 2A and B). In the subgroup with biopsy samples prior to radiochemotherapy (preRCT) OS and NED-survival rates were 54% and 39%. In the subgroup with tumour samples after radiochemotherapy (postRCT) OS and NED-survival rates were 57% and 38% at 8 years. In the postRCT subgroup 30 patients had a pathologically proven complete tumour

Discussion

It is generally accepted that there is an immune suppressive milieu in HNSCC tumours.3, 9 The aim of our study was to evaluate the effect of RCT on inflammatory cells in the tumour after treatment and, more specifically, how the immune suppressive milieu may undergo modifications depending on the extent of tumour regression. To our knowledge, this is the first study to evaluate tumour infiltrating inflammatory cells in HNSCC after RCT comparing the RCT-induced changes with the preRCT data. We

Conflict of interest statement

None declared.

Acknowledgements

We thank Birgit Meyer and Rudolf Jung for excellent technical assistance.

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