MX1 Expression in Cancer Cells Is Strongly Linked to CD8+ T-Cell Infiltration and PD-L1 Expression: A Tissue Microarray Study Evaluating More than 14,000 Tumors from 145 Different Tumor Entities
Benjamin Bajusz, Andrea Hinsch, Seyma Büyücek, Clara von Bargen, Frank Jacobsen, David Dum, Ria Schlichter, Patrick Lebok, Christian Bernreuther, Martina Kluth, Claudia Hube-Magg, Georgia Makrypidi-Fraune, Viktoria Chirico, Piero Caneve, Simon Kind, Guido Sauter, Maximilian Lennartz, Till S. Clauditz, Andreas H. Marx, Waldemar Wilczak, Maria Christina Tsourlakis, Ronald Simon, Stefan Steurer, Sarah Minner, Till Krech, Morton Freytag, Kristina JansenIntroduction: Myxovirus resistance protein 1 (MX1) contributes to resistance against viral infections, including to influenza, and has recently been implicated in cancer. Methods: A tissue microarray with 17,909 samples from 145 tumor types/subtypes and 608 samples from 76 normal tissue types was analyzed by immunohistochemistry (IHC) to assess MX1 expression. Results: MX1 positivity was found in tumor cells of 5956 of 14,512 analyzable samples, and 131 of 145 entities included at least one positive case. High positivity rates occurred in squamous cell carcinomas (up to 88%), neuroendocrine neoplasms (up to 85%), germ cell neoplasms (up to 77%), salivary gland tumors (up to 75%), mesothelioma (up to 74%), endometrial and ovarian carcinomas (up to 73%), cervical adenocarcinoma (73%), pancreatic ductal adenocarcinoma (65%), and urothelial carcinoma (up to 62%). MX1 expression correlated with PD-L1 positivity and CD8+ lymphocyte density (p < 0.0001 each). High MX1 expression was linked to grade progression in breast cancer (p < 0.0001), microsatellite instability in colorectal adenocarcinoma (p = 0.0003), high grade (p = 0.0431) and advanced pT stage (p = 0.0269) in hepatocellular carcinoma, distant metastasis in clear cell renal cell carcinoma (ccRCC, p = 0.0164), and nodal metastasis in papillary RCC (pRCC; p = 0.0326). Low MX1 expression was linked to stage progression in muscle-invasive urothelial carcinoma (p = 0.0372) and colorectal adenocarcinoma (p = 0.0002), papillary (p = 0.013) and follicular (p = 0.0221) thyroid cancer, and nodal metastasis in serous high-grade ovarian carcinoma (p = 0.0355). MX1 expression was unrelated to phenotype in endometrioid endometrial and ovarian carcinoma. Conclusions: MX1 expression in tumors is strongly linked to CD8+ lymphocyte density and PD-L1 expression, suggesting an association with an immune-inflamed, type I interferon-related tumor microenvironment.