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Abstract：
Nasopharyngeal carcinoma (NPC) and oropharyngeal carcinoma (OPC) are subtypes of head and neck cancer with different treatment effects due to the heterogeneity of tumor microenvironments. This study was to investigate the distinctive tumor microenvironments of NPC and OPC. Analyzing single-cell data from 10 cases of each subtype, we reveal significant differences in cellular composition, with NPC microenvironment dominated by T/NK and B cells, and OPC characterized by prevalent epithelial cells and fibroblasts. Dynamic transitions of CD8 T cells are observed in both tumor types, involving shifts from naivety to cytotoxicity, proliferation, and eventual exhaustion/exhausted states. Additionally, Tregs exhibit heightened proliferative abilities in later developmental stages, concomitant with exhaustion. These highly proliferative T cells and Tregs manifest elevated glycolysis and lactate metabolism activities. Furthermore, we explore intercellular communication between glycolytic malignant epithelial cells and these proliferative T cells. These findings offer comprehensive insights into the heterogeneity of tumor microenvironments and provide a solid foundation for future therapeutic strategies and targeted interventions.
摘要：
鼻咽癌（NPC）和口咽癌（OPC）是头颈癌的亚型，由于肿瘤微环境的异质性，其治疗效果不同。本研究旨在探讨NPC和OPC独特的肿瘤微环境。分析每种亚型10例的单细胞数据，我们揭示了细胞组成的显著差异，以T/NK和B细胞为主的NPC微环境，和OPC的特征在于普遍存在的上皮细胞和成纤维细胞。在两种肿瘤类型中都观察到CD8T细胞的动态转变，涉及从天真到细胞毒性的转变，扩散,和最终耗尽/耗尽状态。此外,Tregs在后期发育阶段表现出增强的增殖能力，伴随着疲惫。这些高度增殖的T细胞和Treg表现出升高的糖酵解和乳酸代谢活性。此外，我们探索糖酵解恶性上皮细胞和这些增殖性T细胞之间的细胞间通讯。这些发现为肿瘤微环境的异质性提供了全面的见解，并为未来的治疗策略和有针对性的干预措施提供了坚实的基础。
