Introduction While neoadjuvant radiotherapy is the standard of care in locally invasive rectal carcinoma (LIRC), only half of patients show a response. A predictive test enabling better patient selection could avoid unneccessary radiation exposure to poor responders. Macrophages within the tumour immune microenvironment with tumoricidal M1 and tumour-protective M2 phenotypes could be modulating this response. This study investigated the possible predictive value of M1 and M2 subpopulations in identifying patients’ likely response to short-course preoperative radiotherapy.
Method Biopsy samples were taken from 29 patients with locally invasive rectal carcinoma before treatment with short course radiotherapy and surgical specimens obtained after resection following short-course preoperative radiotherapy. Dual-staining immunohistochemistry was performed with CD68 as macrophage marker, HLA-DR as M1 marker, and CD163 as M2 marker. Samples were scored for hot-and-random spots by Nuance software (version 3.0.2) and compared with patients’ outcome data. Tumour response was measured by assessment of reduction of tumour-cell density.
Results Samples revealing a low score for HLA-DR positive M1 macrophages exhibited a better response to short-course radiotherapy with up to 80% (median 80·38% [IQR 46·94–84·73]) reduction in the tumour cell density. On the other hand those with a high score exhibited a poor response with only up to 20% (20·26 [0–48·19]) reduction. The difference in response between the two groups was significant (p = 0·017). No such trends were observed for CD163+M2 macrophages. The ratio of HLA–DR+ to CD163+macrophages for biopsy and resection samples was significantly different showing a drop in the HLA-DR positive macrophages in the resection samples (p 0.024). The mean of the difference between the biopsy (median 2·53 [IQR 1.98 – 3.08]) and resection (1·38 [IQR 0.96 – 1.8]) was 1·15 (p = 0·024).
Conclusion Patients with a variable macrophage phenotype composition within biopsy samples from patients with locally invasive rectal carcinoma respond differently to short-course preoperative radiotherapy. Further investigation involving a panel of macrophage and other immune-cell markers could verify and validate these findings and develop them as predictive tests identifying good responders to radiotherapy in patients with locally invasive rectal carcinoma.
Disclosure of interest None Declared.
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.