Interferon-stimulated gene 15 (ISG15) is known to be involved in tumor progression. We previously reported that ISG15 expressed on nasopharyngeal carcinoma (NPC) cells and related to poor prognosis of patients with NPC. We further observed that ISG15 can be secreted by NPC cell and expressed on the macrophages in situ. However, the role of ISG15 in tumor-associated macrophages (TAMs) remains poorly understood. In the present study, we found that ISG15 treatment induces macrophages with M2-like phenotype, and the enhancement of NPC cell migration and tumorigenicity. Mechanically, ISG15-induced M2-like phenotype is dependent on the interaction with its receptor, LFA-1, and engagement of SRC family kinase (SFK) signal, and the subsequent secretion of CCL18. Blocking LFA-1, or SRC signal with small molecular inhibitors, or neutralizing with anti-CCL18 antibody can impede the activation of LFA-1-SFK-CCL18 axis in ISG15-treated macrophages. Clinically, ISG15+ CD163+ TAMs related to impaired survival of patients and advanced tumor stage of NPC. Furthermore, we found ISG15+ CD163+ macrophages inhibited antitumor CD8+ cells responses in NPC. Together, our findings suggested tumor cell-secreted ISG15, which acted as a tumor microenvironmental factor, induces M2-like phenotype, promoting tumor progression and suppression of cytotoxic T lymphocyte response.

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PurposeThe present study was designed to retrospectively evaluate the prognostic value of the C-reactive protein/albumin (CRP/ALB) ratio in laryngeal squamous cell carcinoma (LSCC).MethodsOne hundred and twenty-nine newly diagnosed LSCC patients admitted between May 2006 and October 2011 were retrospectively reviewed. Their serum CRP and ALB were quantified preoperatively. The relationship between the CRP/ALB ratio and the clinicopathologic features was analyzed. Receiver operating characteristic curve was used to calculate the prognostic value of the CRP/ALB ratio. Then, the Cox proportional hazards model was used in univariate and multivariate analyses to identify significant prognostic factors associated with disease-free survival and overall survival.ResultsThe cutoff value for CRP/ALB ratio was 0.047. An elevated CRP/ALB ratio was significantly associated with nodal metastasis, late disease stage, and recurrence. Also, high values of CRP/ALB ratio were significant predictors for poor overall survival and disease-free survival on multivariate analysis.ConclusionPretreatment CRP/ALB ratio may be a significant prognostic marker in LSCC.