Tumoral immune-infiltrate (IF), PD-L1 expression and role of CD8/TIA-1 lymphocytes in localized osteosarcoma patients treated within protocol ISG-OS1.
Tumoral immune-infiltrate (IF), PD-L1 expression and role of CD8/TIA-1 lymphocytes in localized osteosarcoma patients treated within protocol ISG-OS1.
复制标题
DOI：
10.18632/oncotarget.22912
复制
发表时间：
2017-12-19
期刊：
影响因子：
--
通讯作者：
Ferrari S
中科院分区：
文献类型：
--
作者：
Palmerini E;Agostinelli C;Picci P;Pileri S;Marafioti T;Lollini PL;Scotlandi K;Longhi A;Benassi MS;Ferrari S
我们假设免疫浸润与上级生存率相关，并检查了原发性骨肉瘤组织微阵列（TMA）来验证这一假设。本研究纳入了129例在方案ISG-OS 1内接受治疗的局部骨肉瘤患者（患者）。分析临床特征、CD 8、CD 3、FOXP 3、CD 20、CD 68/CD 163（肿瘤相关巨噬细胞，TAM）、Tia-1（细胞毒性T细胞）、CD 303（浆细胞样树突状细胞：pDC）、精氨酸酶-1（髓源性抑制细胞：MDSC）、免疫细胞（IC）上的PD-1以及肿瘤细胞（TC）和IC上的PD-L1的表达，并与结局相关。肿瘤浸润淋巴细胞（TIL）占绝大多数（CD 3 + 90%; CD 8 + 86%）。在73%的样品中检测到Tia-1。IC中14%的患者和TC中0%的患者发现PD-L1表达; IC中22%的患者显示PD-1表达。中位随访时间为8年（范围1-13年），5年总生存率（5年OS）为74%（95% CI 64-85）。单变量分析显示：a）对新辅助化疗具有良好组织学应答的患者（p = 0.0001）; B）具有CD 8/Tia 1肿瘤浸润的患者（p = 0.002）; c）具有正常碱性磷酸酶（sALP）的患者（p = 0.04）的5年OS更好。多变量分析后，组织学反应（p = 0.007）和CD 8/Tia 1浸润（p = 0.01）与生存独立相关。在CD 8+浸润患者亚组中，观察到PD-L1（IC）+病例的OS更差（p 0.02）。我们的研究结果支持这样的假设，即诊断时肿瘤微环境中的CD 8/Tia 1浸润赋予局部骨肉瘤患者上级生存率，而PD-L1表达与较差的生存率相关。
We hypothesized that immune-infiltrates were associated with superior survival, and examined a primary osteosarcoma tissue microarrays (TMAs) to test this hypothesis. 129 patients (pts) with localized osteosarcoma treated within protocol ISG-OS1 were included in the study. Clinical characteristics, expression of CD8, CD3, FOXP3, CD20, CD68/CD163 (tumor associated macrophage, TAM), Tia-1 (cytotoxic T cell), CD303 (plasmacytoid dendritic cells: pDC), Arginase-1 (myeloid derived suppressor cells: MDSC), PD-1 on immune-cells (IC), and PD-L1 on tumoral cells (TC) and IC were analysed and correlated with outcome. Most of the cases presented tumor infiltrating lymphocytes (TILs) (CD3+ 90%; CD8+ 86%). Tia-1 was detected in 73% of the samples. PD-L1 expression was found in 14% patients in IC and 0% in TC; 22% showed PD-1 expression in IC. With a median follow-up of 8 years (range 1-13), the 5-year overall survival (5-year OS) was 74% (95% CI 64-85). Univariate analysis showed better 5-year OS for: a) pts with a good histologic response to neoadjuvant chemotherapy (p = 0.0001); b) pts with CD8/Tia1 tumoral infiltrates (p = 0.002); c) pts with normal alkaline phosphatas (sALP) (p = 0.04). After multivariate analysis, histologic response (p = 0.007) and CD8/Tia1 infiltration (p = 0.01) were independently correlated with survival. In the subset of pts with CD8+ infiltrate, worse (p 0.02) OS was observed for PD-L1(IC)+ cases. Our findings support the hypothesis that CD8/Tia1 infiltrate in tumor microenvironment at diagnosis confers superior survival for pts with localized osteosarcoma, while PD-L1 expression is associated with worse survival.
登录
查看更多内容
PD-1，PD-1配体的关联以及肿瘤免疫微环境的其他特征与抗PD-1治疗的响应。
DOI：
10.1158/1078-0432.ccr-13-3271
发表时间：
2014-10-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Taube JM;Klein A;Brahmer JR;Xu H;Pan X;Kim JH;Chen L;Pardoll DM;Topalian SL;Anders RA
通讯作者：
Anders RA
影响因子：
28.2
作者：
Llosa, Nicolas J.;Cruise, Michael;Housseau, Franck
通讯作者：
Housseau, Franck
影响因子：
11.2
作者：
Lyford-Pike S;Peng S;Young GD;Taube JM;Westra WH;Akpeng B;Bruno TC;Richmon JD;Wang H;Bishop JA;Chen L;Drake CG;Topalian SL;Pardoll DM;Pai SI
通讯作者：
Pai SI
影响因子：
64.8
作者：
Herbst RS;Soria JC;Kowanetz M;Fine GD;Hamid O;Gordon MS;Sosman JA;McDermott DF;Powderly JD;Gettinger SN;Kohrt HE;Horn L;Lawrence DP;Rost S;Leabman M;Xiao Y;Mokatrin A;Koeppen H;Hegde PS;Mellman I;Chen DS;Hodi FS
通讯作者：
Hodi FS
影响因子：
28.5
作者：
McCaughan GJ;Fulham MJ;Mahar A;Soper J;Hong AM;Stalley PD;Tattersall MH;Bhadri VA
通讯作者：
Bhadri VA