One of most challenging issues in tumor immunology is a better understanding of the dynamics in the accumulation of myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment (TIME), as this would lead to the development of new cancer therapeutics. Here, we show that translationally controlled tumor protein (TCTP) released by dying tumor cells is an immunomodulator crucial to full-blown MDSC accumulation in the TIME. We provide evidence that extracellular TCTP mediates recruitment of the polymorphonuclear MDSC (PMN-MDSC) population in the TIME via activation of Toll-like receptor-2. As further proof of principle, we show that inhibition of TCTP suppresses PMN-MDSC accumulation and tumor growth. In human cancers, we find an elevation of TCTP and an inverse correlation of TCTP gene dosage with antitumor immune signatures and clinical prognosis. This study reveals the hitherto poorly understood mechanism of the MDSC dynamics in the TIME, offering a new rationale for cancer immunotherapy.

肿瘤免疫学中最具挑战性的问题之一是更好地了解肿瘤微环境 (TIME) 中髓源抑制细胞 (MDSC) 积累的动力学，因为这将导致新的癌症治疗方法的发展。在这里，我们表明，由垂死的肿瘤细胞释放的翻译控制肿瘤蛋白 (TCTP) 是一种免疫调节剂，对于在 TIME 中全面积累 MDSC 至关重要。我们提供的证据表明，细胞外 TCTP 通过激活 Toll 样受体 2 在 TIME 介导多形核 MDSC (PMN-MDSC) 群的募集。作为原理的进一步证明，我们表明抑制 TCTP 可抑制 PMN-MDSC 积累和肿瘤生长。在人类癌症中，我们发现 TCTP 升高以及 TCTP 基因剂量与抗肿瘤免疫特征和临床预后呈负相关。这项研究揭示了迄今为止人们对 TIME 中 MDSC 动力学机制知之甚少，为癌症免疫治疗提供了新的理论基础。