Only 10–30% of oesophageal and rectal adenocarcinoma patients treated with neoadjuvant chemoradiotherapy have a complete pathological response. Inflammatory and angiogenic mediators in the tumour microenvironment (TME) may enable evasion of anti-tumour immune responses. The TME influence on infiltrating dendritic cells (DCs) was modelled by treating immature monocyte-derived DCs with Tumour Conditioned Media (TCM) from distinct gastrointestinal sites, prior to LPS-induced maturation. Cell line conditioned media from gastrointestinal cell lines inhibited LPS-induced DC markers and TNF-α secretion. TCM generated from human tumour biopsies from oesophageal, rectal and colonic adenocarcinoma induced different effects on LPS-induced DC markers - CD54, CD80, HLA-DR, CD86 and CD83 were enhanced by oesophageal cancer; CD80, CD86 and CD83 were enhanced by rectal cancer, whereas CD54, HLA-DR, CD86, CD83 and PD-L1 were inhibited by colonic cancer. Notably, TCM from all GI cancer types inhibited TNF-α secretion. Additionally, TCM from irradiated biopsies inhibited DC markers. Profiling the TCM showed that IL-2 levels positively correlated with maturation marker CD54, while Ang-2 and bFGF levels negatively correlated with CD54. This study identifies that there are differences in DC maturational capacity induced by the TME of distinct gastrointestinal cancers. This could potentially have implications for anti-tumour immunity and response to radiotherapy.

中文翻译：

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上，下胃肠道的肿瘤微环境差异地影响树突状细胞的成熟。

经新辅助放化疗治疗的食道和直肠腺癌患者中只有10–30％具有完全的病理反应。肿瘤微环境（TME）中的炎性和血管生成介质可以逃避抗肿瘤免疫反应。通过在LPS诱导的成熟之前，用来自不同胃肠道的肿瘤条件培养基（TCM）处理未成熟单核细胞衍生的DC，来模拟TME对浸润的树突状细胞（DC）的影响。来自胃肠道细胞系的细胞系条件培养基抑制LPS诱导的DC标志物和TNF-α分泌。食管癌，直肠癌和结肠腺癌的人肿瘤活检产生的中药对LPS诱导的DC标记物具有不同的作用-食管癌会增强CD54，CD80，HLA-DR，CD86和CD83的作用；CD80，直肠癌可增强CD86和CD83，而结肠癌可抑制CD54，HLA-DR，CD86，CD83和PD-L1。值得注意的是，来自所有胃肠道癌症类型的中药均能抑制TNF-α的分泌。另外，来自经放射的活检的TCM抑制了DC标志物。对中药进行分析显示，IL-2水平与成熟标记CD54正相关，而Ang-2和bFGF水平与CD54负相关。这项研究表明，TME诱导的不同胃肠道癌的DC成熟能力存在差异。这可能会影响抗肿瘤免疫力和对放射治疗的反应。对中药进行分析显示，IL-2水平与成熟标记CD54正相关，而Ang-2和bFGF水平与CD54负相关。这项研究表明，TME诱导的不同胃肠道癌的DC成熟能力存在差异。这可能会影响抗肿瘤免疫力和对放射治疗的反应。对中药进行分析显示，IL-2水平与成熟标记CD54正相关，而Ang-2和bFGF水平与CD54负相关。这项研究表明，TME诱导的不同胃肠道癌的DC成熟能力存在差异。这可能会影响抗肿瘤免疫力和对放射治疗的反应。