Cytotoxic and immunosuppressive inflammatory cells predict regression and prognosis following neoadjuvant radiochemotherapy of oesophageal adenocarcinoma

Abstract

Background and purposeTumour infiltrating lymphocytes (TIL) and tumour associated macrophages (TAM) play a key role in anticancer immunosurveillance. We studied their influence on response to neoadjuvant radiochemotherapy (RCT) and prognosis in patients with oesophageal adenocarcinoma (OAC). Materials and methodsBetween 10/2004 and 06/2018, pre-RCT biopsy-specimens were available from 76 patients with locally advanced, non-metastatic OAC scheduled for trimodality therapy. We evaluated intra- and peritumoural expression of FoxP3+-, CD8+-TIL and CD68+-, CD163+-TAM, contemplating cell density, cell ratios and cell-to-cell distances to determine a possible influence on tumour regression grade (TRG) and survival. Median follow-up time for all patients was 18 months (IQR 9–43), and 54 months (25–97) for surviving patients. Data were analysed using risk analysis, logrank test and Cox regression. ResultsPoor tumour regression was detected for cN+ (RR 0.77 [95% CI 0.66–0.90], p = 0.001), low intratumoural FoxP3+/CD8+ ratio (RR 0.75 [0.60–0.96], p = 0.020), high peritumoural CD163+/CD68+ ratio (RR 0.77 [0.60–0.99], p = 0.045) and high intratumoural TAM density (RD −0.44 [−0.82 to −0.06], p = 0.023).Apart from poor resection quality and TRG, pretherapeutic high peritumoural CD8+ infiltration (HR 2.36 [1.21–4.61], p = 0.012) and short intratumoural FoxP3+ to CD8+ cell-to-cell distances in middle ranged CD8+ density (HR 2.55 [1.00–6.52], p = 0.050) were significant unfavourable prognostic factors in multivariate analysis. ConclusionsImmunologic parameters, such as CD8+-, FoxP3+-TIL and CD68+-, CD163+-TAM, were identified to be of independent predictive and prognostic value in patients with OAC. Further and independent validation of these biomarkers by a large size dataset may urgently be contemplated.