抗血管生成抑制剂已被证明可以与免疫检查点阻断产生协同作用，但协同反应的潜在机制尚不完全清楚。我们研究了 VEGFR2 抑制对体内肿瘤浸润免疫细胞的影响，以及阿帕替尼和抗血管生成抑制剂联合用药的活性。 -HNSCC 协同小鼠模型中的 PD-1。 1例左侧舌鳞状细胞癌伴颈部淋巴结患者接受卡瑞利珠单抗和阿帕替尼联合诱导治疗，以验证术前新辅助免疫治疗的疗效。我们发现阿帕替尼增加了CD8 T细胞的浸润，减少了CD8 T细胞的数量。临床前同基因小鼠模型中的 Tregs。在阿帕替尼治疗的肿瘤中，CD8 PD1 T 细胞的比例显着增加。阿帕替尼和抗 PD-1 联合治疗比单独治疗有更好的治疗效果。左舌鳞状细胞癌伴颈部淋巴结患者经过两个周期的联合诱导治疗后达到主要病理缓解（MPR）。我们的研究表明，阿帕替尼治疗与抗 PD-1 抗体在临床前癌症模型中和在临床前癌症模型中具有协同作用。晚期 HNSCC 患者。这些结果为在 HNSCC 大规模临床试验中推进这种新辅助免疫疗法提供了新的理论依据。© 2023 Wiley periodicals LLC。

Antiangiogenic inhibitors have been shown to synergize with immune checkpoint blockade, but the underlying mechanisms of the synergistic response are not fully understood.We investigate the impact of VEGFR2 inhibition on tumor-infiltrating immune cells in vivo and the activity of the combination of apatinib and anti-PD-1 in synergistic mouse model of HNSCC. A patient with squamous cell carcinoma of the left tongue with cervical lymph node were received with combined induction treatment of camrelizumab and apatinib to validate the efficacy of neoadjuvant immunotherapy before surgery.We found that apatinib increased the infiltration of CD8+ T cells and decreased the population of Tregs in a preclinical syngeneic mouse model. The proportions of CD8+ PD1+ T cells were significantly increased in apatinib-treated tumors. The combined treatment of apatinib and anti-PD-1 demonstrated better therapeutic benefit than each treatment alone. The patient with squamous cell carcinoma of the left tongue with cervical lymph node achieved major pathologic response (MPR) after two cycles of combined induction treatment.Our study demonstrated that apatinib therapy synergized with an anti-PD-1 antibody in preclinical cancer models and in patient with advanced HNSCC. These results provide a new rationale for advancing this neoadjuvant immunotherapy in large scale of clinical trials of HNSCC.© 2023 Wiley Periodicals LLC.