食管癌（ESCA）是一种与慢性炎症和免疫失调相关的恶性肿瘤。然而，该疾病的特异性免疫状态和免疫调节的关键机制还需要进一步探索。为了研究人ESCA肿瘤免疫微环境的特征及其可能的调节作用，我们通过飞行时间质谱流式分析、单细胞RNA测序、对组织进行多色荧光染色，并对初治患者的肿瘤和癌旁组织进行流式细胞术分析。我们描绘了 ESCA 的免疫景观，并揭示了 CD8（组织驻留记忆 CD8 T 细胞（CD8 TRM））与疾病密切相关我们还揭示了 ESCA 肿瘤微环境 (TME) 中 CD8 TRM 的异质性，这与其分化和功能有关。此外，肿瘤中表达高水平颗粒酶 B 和免疫的 CD8 TRM 子集（称为 tTRM）。我们证明，晚期 ESCA 的 TME 中的检查点显着减少，tTRM 是 TME 中预激活的肿瘤效应细胞，然后我们证明，源自中间单核细胞 (iMos) 的传统树突状细胞 (cDC2) 对于维持 CD8 TRM 的增殖至关重要。在 TME 中。我们的初步研究表明，缺氧可以促进iMos的凋亡并阻碍cDC2的成熟，从而降低CD8 TRM的增殖能力，从而促进癌症的进展。我们的研究揭示了CD8 TRM的重要抗肿瘤作用，并初步揭示了CD8 TRM的抗肿瘤作用。探索了人类 ESCA TME 中 iMo/cDC2/CD8 TRM 免疫轴的调节。© 作者（或其雇主）2024。在 CC BY-NC 下允许重复使用。不得商业再利用。请参阅权利和权限。英国医学杂志出版。

Esophageal cancer (ESCA) is a form of malignant tumor associated with chronic inflammation and immune dysregulation. However, the specific immune status and key mechanisms of immune regulation in this disease require further exploration.To investigate the features of the human ESCA tumor immune microenvironment and its possible regulation, we performed mass cytometry by time of flight, single-cell RNA sequencing, multicolor fluorescence staining of tissue, and flow cytometry analyses on tumor and paracancerous tissue from treatment-naïve patients.We depicted the immune landscape of the ESCA and revealed that CD8+ (tissue-resident memory CD8+ T cells (CD8+ TRMs) were closely related to disease progression. We also revealed the heterogeneity of CD8+ TRMs in the ESCA tumor microenvironment (TME), which was associated with their differentiation and function. Moreover, the subset of CD8+ TRMs in tumor (called tTRMs) that expressed high levels of granzyme B and immune checkpoints was markedly decreased in the TME of advanced ESCA. We showed that tTRMs are tumor effector cells preactivated in the TME. We then demonstrated that conventional dendritic cells (cDC2s) derived from intermediate monocytes (iMos) are essential for maintaining the proliferation of CD8+ TRMs in the TME. Our preliminary study showed that hypoxia can promote the apoptosis of iMos and impede the maturation of cDC2s, which in turn reduces the proliferative capacity of CD8+ TRMs, thereby contributing to the progression of cancer.Our study revealed the essential antitumor roles of CD8+ TRMs and preliminarily explored the regulation of the iMo/cDC2/CD8+ TRM immune axis in the human ESCA TME.© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.