The effect of neoadjuvant radiotherapy on immune cell infiltrates in myxofibrosarcoma

Myxofibrosarcoma (MFS) is a subtype of soft-tissue sarcoma for which local treatment includes neoadjuvant radiotherapy (nRT) followed by surgery. The impact of nRT on the MFS tumor immune microenvironment remains unexplored.

Paired pre-nRT biopsy and post-nRT surgery samples from 31 MFS patients were retrospectively collected. The intratumoral density of T cells, cytotoxic T cells, regulatory T cells, helper T cells, B cells and natural killer (NK) cells and expression of programmed death-ligand 1 were quantified using multiplex immunohistochemistry (mIHC). mIHC marker densities were compared between pre- and post-nRT samples, and their associations with clinicopathological characteristics and patient outcomes were assessed.

There was substantial interpatient heterogeneity in mIHC marker densities, both pre- and post-nRT. A significant reduction in cytotoxic T cell {205 [interquartile range (IQR) 674] pre-nRT versus 58 (IQR 205) post-nRT, P = 0.030} and helper T cell [220 (IQR 343) pre-nRT versus 74 (IQR 110) post-nRT, P = 0.011] densities, alongside an increase in NK cell [2 (IQR 8) pre-nRT versus 7 (IQR 16) post-nRT, P = 0.050] infiltration, was observed following nRT. There were no statistically significant associations between mIHC marker densities measured before or after nRT, or their changes over time, and patient outcomes.

Conventional nRT is associated with reduced cytotoxic and helper T cell infiltration and increased presence of NK cells in MFS. These results suggest that conventional nRT reduces inflammatory aspects of MFS tumors.