Immunotherapies have become the first line of treatment for many cancer types. Unfortunately, only a small fraction of patients benefits from these therapies. This low rate of success can be attributed to 3 main barriers: 1) low frequency of anti-tumor specific T cells; 2) lack of infiltration of the anti-tumor specific T cells into the tumor parenchyma and 3) accumulation of highly suppressive cells in the tumor mass that inhibit the effector function of the anti-tumor specific T cells. Thus, the identification of immunomodulators that can increase the frequency and/or the infiltration of antitumor specific T cells while reducing the suppressive capacity of the tumor microenvironment is necessary to ensure the effectiveness of T cell immunotherapies.

In this review, we discuss the potential of poly-ICLC as a multi-functional immune modulator for treating cancer and its impact on the 3 above mentioned barriers. We describe the unique capacity of poly-ICLC in stimulating 2 separate pattern recognition receptors, TLR3 and cytosolic MDA5 and the consequences of these activations on cytokines and chemokines production. We emphasize the role of poly-ICLC as an adjuvant in the setting of peptide-based cancer vaccines and in situ tumor vaccination by mimicking natural immune responses to infections. Finally, we summarize the impact of poly-ICLC in enhancing T infiltration into the tumor parenchyma and address the implication of this finding in the clinic.

免疫疗法已成为许多癌症类型的一线治疗方法。不幸的是，只有一小部分患者从这些疗法中受益。这种低成功率可归因于 3 个主要障碍：1) 抗肿瘤特异性 T 细胞的频率低；2) 缺乏抗肿瘤特异性 T 细胞对肿瘤实质的浸润和 3) 肿瘤块中高度抑制性细胞的积累，这些细胞抑制了抗肿瘤特异性 T 细胞的效应功能。因此，鉴定可以增加抗肿瘤特异性 T 细胞的频率和/或浸润同时降低肿瘤微环境抑制能力的免疫调节剂对于确保 T 细胞免疫疗法的有效性是必要的。

在这篇综述中，我们讨论了 poly-ICLC 作为治疗癌症的多功能免疫调节剂的潜力及其对上述 3 个障碍的影响。我们描述了 poly-ICLC 在刺激 2 个独立的模式识别受体 TLR3 和胞质 MDA5 方面的独特能力，以及这些激活对细胞因子和趋化因子产生的影响。我们强调了 poly-ICLC 作为佐剂在基于肽的癌症疫苗和原位肿瘤疫苗接种中的作用，通过模拟对感染的自然免疫反应。最后，我们总结了 poly-ICLC 在增强 T 浸润到肿瘤实质中的影响，并解决了这一发现在临床中的意义。