Lapeyre-Prost A, Terme M, Pernot S, Pointet A-L, Voron T, Tartour E, Taieb J
INSERM U970, PARCC (Paris Cardiovascular Research Center), Université Paris-Descartes, Paris, France.
INSERM U970, PARCC (Paris Cardiovascular Research Center), Université Paris-Descartes, Paris, France.
Int Rev Cell Mol Biol. 2017;330:295-342. doi: 10.1016/bs.ircmb.2016.09.007. Epub 2016 Dec 26.
The ability of tumor cells to escape tumor immunosurveillance contributes to cancer development. Factors produced in the tumor microenvironment create "tolerizing" conditions and thereby help the tumor to evade antitumoral immune responses. VEGF-A, already known for its major role in tumor vessel growth (neoangiogenesis), was recently identified as a key factor in tumor-induced immunosuppression. In particular, VEGF-A fosters the proliferation of immunosuppressive cells, limits T-cell recruitment into tumors, and promotes T-cell exhaustion. Antiangiogenic therapies have shown significant efficacy in patients with a variety of solid tumors, preventing tumor progression by limiting tumor-induced angiogenesis. VEGF-targeting therapies have also been shown to modulate the tumor-induced immunosuppressive microenvironment, enhancing Th1-type T-cell responses and increasing tumor infiltration by T cells. The immunomodulatory properties of VEGF-targeting therapies open up new perspectives for cancer treatment, especially through strategies combining antiangiogenic drugs with immunotherapy. Preclinical models and early clinical studies of these combined approaches have given promising results.
肿瘤细胞逃避免疫监视的能力有助于癌症的发展。肿瘤微环境中产生的因子创造了“耐受”条件，从而帮助肿瘤逃避抗肿瘤免疫反应。血管内皮生长因子A（VEGF-A），因其在肿瘤血管生成（新生血管形成）中的主要作用而闻名，最近被确定为肿瘤诱导免疫抑制的关键因素。特别是，VEGF-A促进免疫抑制细胞的增殖，限制T细胞向肿瘤的募集，并促进T细胞耗竭。抗血管生成疗法已在多种实体瘤患者中显示出显著疗效，通过限制肿瘤诱导的血管生成来防止肿瘤进展。靶向VEGF的疗法也已被证明可调节肿瘤诱导的免疫抑制微环境，增强Th1型T细胞反应并增加T细胞对肿瘤的浸润。靶向VEGF疗法的免疫调节特性为癌症治疗开辟了新的前景，特别是通过将抗血管生成药物与免疫疗法相结合的策略。这些联合方法的临床前模型和早期临床研究已取得了有希望的结果。
