Neoadjuvant radiochemotherapy significantly alters the phenotype of plasmacytoid dendritic cells and 6-sulfo LacNAc+ monocytes in rectal cancer

Neoadjuvant radiochemotherapy (nRCT) can significantly influence the tumor immune architecture that plays a pivotal role in regulating tumor growth. Whereas various studies have investigated the effect of nRCT on tumor-infiltrating T cells, little is known about its impact on the frequency and activation status of human dendritic cells (DCs). Plasmacytoid DCs (pDCs) essentially contribute to the regulation of innate and adaptive immunity and may profoundly influence tumor progression. Recent studies have revealed that higher pDC numbers are associated with poor prognosis in cancer patients. 6-sulfo LacNAc-expressing monocytes (slanMo) represent a particular proinflammatory subset of human non-classical blood monocytes that can differentiate into DCs. Recently, we have reported that activated slanMo produce various proinflammatory cytokines and efficiently stimulate natural killer cells and T lymphocytes. slanMo were also shown to accumulate in clear cell renal cell carcinoma and in metastatic lymph nodes from cancer patients.
In the present study, we investigated the influence of nRCT on frequency and phenotype of rectal cancer-infiltrating pDCs and slanMo. When evaluating rectal cancer tissues obtained from patients after nRCT, a significantly higher frequency of pDCs in comparison to non-matched pre-nRCT tissue samples was found. In contrast, the density of slanMo was not significantly altered by nRCT. These findings were confirmed when analyzing matched pre-nRCT and post-nRCT rectal cancer specimens. Further studies revealed that nRCT significantly increases the percentage of mature CD83+ pDCs in rectal cancer tissues. Moreover, the proportion of pDCs locally expressing interferon-alpha, which plays a major role in antitumor immunity, was significantly higher in post-nRCT. In addition, nRCT markedly enhanced the percentage of inducible nitric oxide synthase- or tumor necrosis factor alpha-producing slanMo in rectal cancer tissues. These novel findings indicate that nRCT significantly influences the frequency and/or phenotype of pDCs and slanMo, which may influence the clinical response of rectal cancer patients to nRCT.