肺腺癌是肺癌中最常见的类型。我们最近报道称，炎症驱动型肺腺癌（IDLA）来源于肺泡Ⅱ型细胞（AT-II细胞），这依赖于主要组织相容性复合物（MHC）II类来促进调节性T细胞扩张。MHCII相关不变链（CD74）与巨噬细胞迁移抑制因子（MIF）结合，与促进肿瘤生长和侵袭相关。然而，MIF-CD74在肺腺癌进展中的作用及其潜在机制仍不清楚。我们旨在探究MIF-CD74在肺腺癌进展中的作用，并阐明肿瘤坏死因子（TNF）-α介导的炎症如何调节IDLA中CD74和MIF表达的机制。在人肺腺癌中，CD74在AT-II细胞来源的肿瘤细胞表面上调高，与淋巴结转移、肿瘤来源/淋巴结受累/转移分期和TNF-α表达呈正相关。MIF与CD74相互作用促进A549和H1299细胞的增殖和迁移。使用尿素诱导的IDLA小鼠模型，我们观察到CD74在肿瘤细胞和巨噬细胞中上调。MIF在IDLA中巨噬细胞中上调。阻断TNF-α依赖性炎症会降低IDLA中肿瘤细胞和巨噬细胞中CD74表达。从A549细胞或激活的小鼠AT-II细胞中获得的条件培养基通过分泌TNF-α在巨噬细胞中上调MIF。TNF-α依赖性肺炎通过上调CD74和MIF表达促进肺腺癌进展，并且AT-II细胞通过分泌TNF-α在巨噬细胞中上调MIF表达。该研究提供了有关CD74在IDLA进展中的功能的新见解。版权所有©2022年美国和加拿大病理学院。Elsevier Inc.发表。保留所有权利。

Lung adenocarcinoma is the most common type of lung cancer. We recently reported that inflammation-driven lung adenocarcinoma (IDLA) originates from alveolar type (AT)-II cells, which depend on major histocompatibility complex (MHC) class II to promote the expansion of regulatory T cells. The MHC class II-associated invariant chain (CD74) binds to the macrophage migration inhibitory factor (MIF), which is associated with promoting tumor growth and invasion. However, the role of MIF-CD74 in the progression of lung adenocarcinoma and the underlying mechanisms remain unclear. We aimed to explore the role of MIF-CD74 in the progression of lung adenocarcinoma and elucidate the mechanisms by which tumor necrosis (TNF)-α-mediated inflammation regulates CD74 and MIF expression in IDLA. In human lung adenocarcinoma, CD74 was upregulated on the surface of tumor cells originating from AT-II cells, which correlated positively with lymph node metastasis, tumor origin/nodal involvement/metastasis stage, and TNF-α expression. MIF interaction with CD74 promoted the proliferation and migration of A549 and H1299 cells in vitro. Using a urethane-induced IDLA mouse model, we observed that CD74 was upregulated in tumor cells and macrophages. MIF expression was upregulated in macrophages in IDLA. Blocking TNF-α-dependent inflammation downregulated CD74 expression in tumor cells and CD74 and MIF expression in macrophages in IDLA. Conditioned medium from A549 cells or activated mouse AT-II cells upregulated MIF in macrophages by secreting TNF-α. TNF-α-dependent lung inflammation contributes to the progression of lung adenocarcinoma by upregulating CD74 and MIF expression, and AT-II cells upregulate MIF expression in macrophages by secreting TNF-α. This study provides novel insights into the function of CD74 in the progression of IDLA.Copyright © 2022 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.