Receptor for activated C kinase 1 (RACK1) has been shown to promote oral squamous cell carcinoma (OSCC) progression, and RACK1 expression levels have been negatively correlated with prognosis in patients with OSCC. Here, we investigated the impact of RACK1 OSCC expression on the recruitment and differentiation of tumor-associated macrophages. High RACK1 expression in OSCC cells correlated with increased M2 macrophage infiltration in tumor samples from a clinical cohort study. Moreover, the combination of RACK1 expression and the M2/M1 ratio could successfully predict prognosis in OSCC. OSCC cells with high RACK1 expression inhibited the migration of THP-1 cells, promoted M2-like macrophage polarization in vitro, and increased the proportion of M2-like macrophages in a xenograft mouse model. Moreover, both M1- and M2-like macrophage polarization-associated proteins were induced in macrophages cocultured with RACK1-silenced cell supernatant. A mechanistic study revealed that the expression and secretion of C-C motif chemokine 2 (CCL2), C-C motif chemokine 5 (CCL5), interleukin-6 (IL-6), and interleukin-1 (IL-1) are closely related to RACK1 expression. In addition, blocking nuclear factor-kappa B (NF-κB) could promote M2-like macrophage polarization. These results indicate that RACK1 and the M2/M1 ratio are predictors of a poor prognosis in OSCC. RACK1 promotes M2-like polarization by regulating NF-κB and could be used as a potential therapeutic target for antitumor immunity.

中文翻译：

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在口腔鳞状细胞癌中，RACK1 通过 NF-κB 通路增加 M2/M1 巨噬细胞比率，从而促进癌症进展。

活化 C 激酶 1 (RACK1) 受体已被证明可促进口腔鳞状细胞癌 (OSCC) 进展，并且 RACK1 表达水平与 OSCC 患者的预后呈负相关。在这里，我们研究了 RACK1 OSCC 表达对肿瘤相关巨噬细胞的招募和分化的影响。OSCC 细胞中 RACK1 的高表达与临床队列研究中肿瘤样本中 M2 巨噬细胞浸润的增加相关。此外，RACK1表达和M2/M1比值的结合可以成功预测OSCC的预后。高表达RACK1的OSCC细胞抑制THP-1细胞的迁移，促进体外M2样巨噬细胞极化，并增加异种移植小鼠模型中M2样巨噬细胞的比例。此外，在与 RACK1 沉默的细胞上清液共培养的巨噬细胞中，M1 和 M2 样巨噬细胞极化相关蛋白均被诱导。机制研究表明CC基序趋化因子2（CCL2）、CC基序趋化因子5（CCL5）、白细胞介素6（IL-6）和白细胞介素1（IL-1）的表达和分泌与RACK1表达密切相关。此外，阻断核因子-κB (NF-κB) 可以促进 M2 样巨噬细胞极化。这些结果表明 RACK1 和 M2/M1 比值是 OSCC 预后不良的预测因子。RACK1 通过调节 NF-κB 促进 M2 样极化，可作为抗肿瘤免疫的潜在治疗靶点。