Phenotypic and Genomic Determinants of Immunotherapy Response Associated with Squamousness
Phenotypic and Genomic Determinants of Immunotherapy Response Associated with Squamousness
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DOI：
10.1158/2326-6066.cir-18-0716
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发表时间：
2019-06-01
影响因子：
10.1
通讯作者：
Kurzrock, Razelle
中科院分区：
文献类型：
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作者：
Goodman, Aaron M.;Kato, Shumei;Kurzrock, Razelle
晚期和转移性鳞状细胞癌（SCC）是常见且难治的恶性肿瘤。我们评估了来自2，651名患者的临床注释数据库的75名免疫治疗的SCC患者，以及来自去识别数据库的9，407名患者，以了解可能影响检查点阻断反应的分子特征。SCC的肿瘤突变负荷（TMB）高于非SCC（P < 0.0001）。皮肤SCC具有最高的TMB（P < 0.0001），其中41.3%显示非常高的TMB（>= 50个突变/Mb）。在免疫治疗的SCC患者中，较高的TMB（>= 12个突变/Mb）与较高的临床获益率[疾病稳定>= 6个月或部分/完全缓解; 60% vs. 29%;（高vs.低TMB）; P = 0.06]和显著较长的中位治疗失败时间（TTF; 9.9 vs. 4.4个月; P = 0.0058）相关。皮肤SCC具有最高的临床获益[11/15例患者（73%）vs. 20/60例（33%）非皮肤SCC（P = 0.008）]、TTF（P = 0.0015）和免疫疗法治疗的总生存期（P =0.06）。总之，在一组不同的SCC中，较高的TMB和皮肤疾病与较好的免疫治疗结果相关。
Advanced and metastatic squamous cell carcinomas (SCC) are common and difficult-to-treat malignancies. We assessed 75 immunotherapy-treated patients with SCC from a clinically annotated database of 2,651 patients, as well as 9,407 patients from a deidentified database for molecular features that might influence checkpoint blockade response. SCCs had higher tumor mutational burdens (TMB) than non-SCCs (P < 0.0001). Cutaneous SCCs had the highest TMB (P < 0.0001), with 41.3% demonstrating a very high TMB (>= 50 mutations/Mb). In immunotherapy-treated patients with SCC, higher TMB (>= 12 mutations/Mb) correlated with a trend to higher clinical benefit rate [stable disease >= 6 months or partial/complete remission; 60% vs. 29%; (high vs. low TMB); P = 0.06] and significantly longer median time-to-treatment failure (TTF; 9.9 vs. 4.4 months; P = 0.0058). Cutaneous SCCs had the highest clinical benefit [11/15 patients (73%) vs. 20/60 (33%) non-cutaneous (P = 0.008)], TTF (P = 0.0015), and overall survival (P =0.06) with immunotherapy treatment. In conclusion, among a diverse set of SCCs, higher TMB and cutaneous disease associated with better immunotherapy outcome.