当前位置: X-MOL 学术Oncoimmunology › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Batf3+ DCs and type I IFN are critical for the efficacy of neoadjuvant cancer immunotherapy.
OncoImmunology ( IF 7.2 ) Pub Date : 2019-02-05 , DOI: 10.1080/2162402x.2018.1546068
Jing Liu 1 , Elisa A Rozeman 2 , Jake S O'Donnell 1, 3, 4 , Stacey Allen 1 , Lorenzo Fanchi 2 , Mark J Smyth 3, 4 , Christian U Blank 2 , Michele W L Teng 1, 4
Affiliation  

New clinical trials are now evaluating the efficacy of neoadjuvant immunotherapy in the context of primary tumor surgery. Using the orthotopic 4T1.2 mouse model of spontaneously metastatic mammary cancer, we have shown that neoadjuvant immunotherapy and surgery was superior in the generation of tumor-specific CD8+ T cells and eradication of lethal metastases compared to surgery followed by adjuvant immunotherapy. However, the importance of host Batf3 and type I interferon (IFN) for long-term survival of mice following neoadjuvant immunotherapy is unknown. Here we demonstrated that loss of Batf3+ DCs or type I IFN receptor blockade in 4T1.2 tumor-bearing mice treated with neoadjuvant anti-PD-1+anti-CD137 immunotherapy reduced long-term survival with a corresponding reduction in tumor-specific CD8+ T cells producing effector cytokines in the primary tumor and in the periphery. Interestingly, we found all high-risk stage III melanoma patients relapsing after adjuvant or neoadjuvant ipilimumab+nivolumab within the OpACIN trial (NCT02437279) displayed low expression of Batf3+ DC-associated genes in pre-treatment tumor biopsies. Further focus should now be placed on validating the requirement of an intratumoral Batf3+ DC gene signature for response to neoadjuvant immunotherapy.

中文翻译:

Batf3 + DC和I型干扰素对于新辅助癌症免疫疗法的疗效至关重要。

现在,新的临床试验正在评估在原发性肿瘤手术中新辅助免疫疗法的疗效。使用自发转移性乳腺癌的原位4T1.2小鼠模型,我们显示与手术后再进行辅助免疫疗法相比,新辅助免疫疗法和手术在肿瘤特异性CD8 + T细胞的产生和致死转移的根除方面更胜一筹。然而,宿主Batf3和I型干扰素(IFN)对新辅助免疫治疗后小鼠长期存活的重要性尚不明确。在这里,我们证明了4T1中Batf3 + DC丢失或I型IFN受体阻滞。用新辅助抗PD-1 +抗CD137免疫疗法治疗的2只荷瘤小鼠降低了长期存活率,相应地减少了在原发性肿瘤和周围区域产生效应细胞因子的肿瘤特异性CD8 + T细胞。有趣的是,我们发现在OpACIN试验(NCT02437279)中,在佐剂或新佐剂ipilimumab + nivolumab后复发的所有高危III期黑色素瘤患者在治疗前的肿瘤活检中均显示Batf3 + DC相关基因的低表达。现在应将更多的重点放在验证肿瘤内Batf3 + DC基因签名对新辅助免疫疗法反应的需求上。我们在OpACIN试验(NCT02437279)中发现所有在佐剂或新佐剂ipilimumab + nivolumab后复发的高危III期黑色素瘤患者在治疗前的肿瘤活检中均显示Batf3 + DC相关基因的低表达。现在应将更多的重点放在验证肿瘤内Batf3 + DC基因签名对新辅助免疫疗法反应的需求上。我们在OpACIN试验(NCT02437279)中发现所有在佐剂或新佐剂ipilimumab + nivolumab后复发的高危III期黑色素瘤患者在治疗前的肿瘤活检中均显示Batf3 + DC相关基因的低表达。现在应将更多的重点放在验证对新辅助免疫疗法应答的肿瘤内Batf3 + DC基因签名的要求上。
更新日期:2018-11-22
down
wechat
bug