Hong Shanjuan, Yuan Qing, Xia Haizhui, Dou Yuan, Sun Tiantian, Xie Tian, Zhang Zhiyin, He Wei, Dong Chen, Lu Jian, Guo Li, Ni Ling
Institute for Immunology and School of Medicine, Tsinghua University, Beijing, China.
Department of Urology, The Third Medical Center of Chinese Peoples Liberation Army (PLA) General Hospital, Beijing, China.
Front Oncol. 2022 Apr 6;12:851191. doi: 10.3389/fonc.2022.851191. eCollection 2022.
There are many potential immunotherapeutic targets for cancer immunotherapy, which should be assessed for efficacy before they enter clinical trials. Here we established an cultured patient-derived tumor tissue model to evaluate antitumor effectiveness of one VISTA inhibitor, given that our previous study showed that VISTA was selectively highly expressed in human clear cell renal cell carcinoma (ccRCC) tumors. We observed that all the tested patients responded to the anti-VISTA monoclonal antibody as manifested by TNF-α production, but only a small fraction were responders to the anti-PD-1 antibody. Co-blockade of VISTA and PD-1 resulted in a synergistic effect in 20% of RCC patients. Taken together, these findings indicate that this tumor slice culture model represents a viable tool to evaluate antitumor efficacies for the inhibitors of immune checkpoints and further supports that VISTA could serve as a promising target for immunotherapy in ccRCC.
癌症免疫疗法有许多潜在的免疫治疗靶点,在进入临床试验之前,应对其疗效进行评估。鉴于我们之前的研究表明VISTA在人透明细胞肾细胞癌(ccRCC)肿瘤中选择性高表达,在此我们建立了一种培养的患者来源肿瘤组织模型,以评估一种VISTA抑制剂的抗肿瘤效果。我们观察到,所有受试患者均对抗VISTA单克隆抗体有反应,表现为肿瘤坏死因子-α的产生,但只有一小部分患者对抗PD-1抗体有反应。VISTA和PD-1的联合阻断在20%的RCC患者中产生了协同效应。综上所述,这些发现表明,这种肿瘤切片培养模型是评估免疫检查点抑制剂抗肿瘤疗效的可行工具,并进一步支持VISTA可作为ccRCC免疫治疗的一个有前景的靶点。