Radiochemotherapy induces a favourable tumour infiltrating inflammatory cell profile in head and neck cancer
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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2023, International Review of Cell and Molecular BiologyOnodera's prognostic nutritional index correlates with tumor immune environment and survival in patients with oral squamous cell carcinoma undergoing chemoradiotherapy
2020, Translational OncologyCitation Excerpt :Tabachnyk et al. demonstrated that tumor-infiltrating CD8+ and granzyme B+ cytotoxic cell counts only slightly decreased compared with other tumor-infiltrating inflammatory cells after neoadjuvant chemoradiotherapy. The authors therefore suggested that CRT provides a favorable antitumor immune environment for patients with residual tumors in HNSCC carcinoma [44]. Recently, Lee et al. [45] reported that patients with high OPNI had a higher CR rate after the primary treatment for follicular lymphoma.
Priming the tumor immune microenvironment with chemo(radio)therapy: A systematic review across tumor types
2020, Biochimica et Biophysica Acta - Reviews on CancerCitation Excerpt :Based on the matched sequentially obtained tumor specimens a significant increase was detected in the following tumor types: rectal cancer treated with fluoropyrimidine based nCRT or nRT (n = 3) [20,38,82], gastric cancer (T2 tumors) treated with carboplatin/paclitaxel based nCRT (n = 1) [22], ovarian cancer treated with carboplatin/paclitaxel based nCT (n = 1) [37], glioblastoma treated with adjuvant temozolomide and RT (n = 1) [74], and pleural mesothelioma treated with platinum/permetrexed based nCT (n = 1) [77]. A significant decrease was observed after treatment with 5-FU/cisplatin based nCRT for oral cavity squamous cell carcinoma (n = 1) [96]. The articles reporting on the difference between a treated (vs. untreated) cohort found a significantly higher number of CD3+ cells in the treated group of the following tumor types: non-small cell lung cancer treated with carboplatin/paclitaxel (n = 1) [113], and colorectal carcinoma liver metastases pre-treated with FOLFOX + Cetuximab (n = 1) [102].
Radioimmunotherapy for the treatment of head and neck cancer
2019, The Lancet OncologyComputer-assisted image analysis of the tumor microenvironment on an oral tongue squamous cell carcinoma tissue microarray
2019, Clinical and Translational Radiation OncologyUtility of CD8 score by automated quantitative image analysis in head and neck squamous cell carcinoma
2018, Oral OncologyCitation Excerpt :Many studies relied on manual counts from acquired still images or examining stained samples directly with a conventional light microscope. One group of authors utilized software (Count from Biomas) to perform cell counting [11,21]. The output of prior quantification studies in TILs in HNSCC has typically been reported as an absolute count of T cells or percentage/ratio to other immune cells.
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These authors contributed equally to this work.