Cisplatin Alters Antitumor Immunity and Synergizes with PD-1/PD-L1 Inhibition in Head and Neck Squamous Cell Carcinoma.
Cisplatin Alters Antitumor Immunity and Synergizes with PD-1/PD-L1 Inhibition in Head and Neck Squamous Cell Carcinoma.
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DOI：
10.1158/2326-6066.cir-17-0235
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发表时间：
2017-12
影响因子：
10.1
通讯作者：
Schmitt NC
中科院分区：
文献类型：
--
作者：
Tran L;Allen CT;Xiao R;Moore E;Davis R;Park SJ;Spielbauer K;Van Waes C;Schmitt NC
头颈部鳞状细胞癌(HNSCC)的顺铂化疗已有数十年的历史，抗PD-1免疫疗法最近已被批准用于该疾病的治疗。然而，关于顺铂单独或联合免疫治疗如何影响HNSCC抗肿瘤免疫的临床前研究尚不多见。在这里，我们表明，在体外，亚致死剂量的顺铂可能会增强抗原呈递和T细胞杀伤，尽管顺铂也会上调肿瘤细胞PD-L1的表达，并可能在较高剂量下损害T细胞的功能。在HNSCC的同基因小鼠模型中，同时使用顺铂和抗PD-L1/PD-1可以延缓肿瘤的生长和提高存活率，而不会显著减少肿瘤浸润性免疫细胞的数量或功能，也不会增加顺铂诱导的毒性。这些结果表明，中等剂量的顺铂可能通过直接杀伤肿瘤细胞以外的机制增强抗肿瘤免疫，而抗PD-L1/PD-1治疗可能进一步增强抗肿瘤免疫。
Head and neck squamous cell carcinoma (HNSCC) has been treated for decades with cisplatin chemotherapy, and anti–PD-1 immunotherapy has recently been approved for the treatment of this disease. However, preclinical studies of how antitumor immunity in HNSCC is affected by cisplatin alone or in combination with immunotherapies are lacking. Here, we show that sublethal doses of cisplatin may enhance antigen presentation and T-cell killing in vitro, though cisplatin also upregulates tumor cell expression of PD-L1 and may impair T-cell function at higher doses. In a syngeneic mouse model of HNSCC, concurrent use of cisplatin and anti–PD-L1/PD-1 delayed tumor growth and enhanced survival without significantly reducing the number or function of tumor-infiltrating immune cells or increasing cisplatin-induced toxicities. These results suggest that moderate doses of cisplatin may enhance antitumor immunity by mechanisms other than direct tumor cell killing, which may be further enhanced by anti–PD-L1/PD-1 therapy.