软组织肉瘤(STS)的代谢升高,18F-氟脱氧葡萄糖正电子发射断层扫描(18F-FDG-PET/CT)与细胞增殖有关,更高等级,和较低的生存。然而,最近针对STS患者的诊断创新(CINSARC基因表达特征和三级淋巴结构[TLS])和治疗创新(免疫检查点抑制剂[ICIs])强调需要重新评估18F-FDG-PET/CT的作用.因此,在这封信中,我们的目的是研究通过核成像评估的STS代谢之间的相关性,和通过转录组学分析估计的免疫景观,免疫组织化学面板,TLS评估。基于在NEOSARCOMICS试验(NCT02789384)中招募的85名患有高级别STS的成人患者的前瞻性队列,我们根据18F-FDG-PET/CT指标确定了3个代谢组(低代谢[60%],-中等[15.3%]和高[24.7%])。我们发现T细胞CD8途径在高代谢STS中显著富集。相反,参与抗肿瘤免疫反应的几种途径,细胞分化和细胞周期,在极低代谢的STS中下调。接下来,多重免疫荧光显示CD8+的密度,CD14+,CD45+,CD68+,与低代谢组相比,高代谢组的c-MAF细胞明显更高。最后,在代谢组和TLS状态之间未发现相关性.总的来说,这些结果表明(i)快速增殖和代谢活跃的STS可以激发更强大的免疫反应,从而吸引免疫细胞,如T细胞和巨噬细胞,和(ii)代谢活性和TLS可以独立地影响免疫应答。
Metabolic elevation in soft-tissue sarcomas (STS), as documented with 18F-Fluorodeoxyglucose positron emission tomography (18F-FDG-PET/CT) has been linked with cell proliferation, higher grade, and lower survivals. However, the recent diagnostic innovations (CINSARC gene-expression signature and tertiary lymphoid structure [TLS]) and therapeutic innovations (immune checkpoint inhibitors [ICIs]) for STS patients underscore the need to re-assess the role of 18F-FDG-PET/CT. Thus, in this correspondence, our objective was to investigate the correlations between STS metabolism as assessed by nuclear imaging, and the immune landscape as estimated by transcriptomics analysis, immunohistochemistry panels, and TLS assessment. Based on a prospective cohort of 85 adult patients with high-grade STS recruited in the NEOSARCOMICS
trial (NCT02789384), we identified 3 metabolic groups according to 18F-FDG-PET/CT metrics (metabolic-low [60%], -intermediate [15.3%] and high [24.7%]). We found that T-cells CD8 pathway was significantly enriched in metabolic-high STS. Conversely, several pathways involved in antitumor immune response, cell differentiation and cell cycle, were downregulated in extreme metabolic-low STS. Next, multiplex immunofluorescence showed that densities of CD8+, CD14+, CD45+, CD68+, and c-MAF cells were significantly higher in the metabolic-high group compared to the metabolic-low group. Lastly, no association was found between metabolic group and TLS status. Overall, these results suggest that (i) rapidly proliferating and metabolically active STS can instigate a more robust immune response, thereby attracting immune cells such as T cells and macrophages, and (ii) metabolic activity and TLS could independently influence immune responses.