Chemotherapy induces dynamic immune responses in breast cancers that impact treatment outcome.
Chemotherapy induces dynamic immune responses in breast cancers that impact treatment outcome.
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化学疗法诱导乳腺癌的动态免疫反应，从而影响治疗结果。
DOI：
10.1038/s41467-020-19933-0
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发表时间：
2020-12-02
影响因子：
16.6
通讯作者：
Kan Z
中科院分区：
文献类型：
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作者：
Park YH;Lal S;Lee JE;Choi YL;Wen J;Ram S;Ding Y;Lee SH;Powell E;Lee SK;Yu JH;Ching KA;Nam JY;Kim SW;Nam SJ;Kim JY;Cho SY;Park S;Kim J;Hwang S;Kim YJ;Bonato V;Fernandez D;Deng S;Wang S;Shin H;Kang ES;Park WY;Rejto PA;Bienkowska J;Kan Z
为了阐明新辅助化疗 (NAC) 的效果，我们对 146 名患者的纵向乳腺癌队列进行了全转录组分析和组织病理学分析，其中包括治疗前、第一个治疗周期后和手术时收集的 110 对连续肿瘤活检样本。在这里，我们证明细胞毒性化疗会引起肿瘤免疫微环境的动态变化，这种变化因亚型和病理反应而异。仅一个周期的治疗即可诱导一种免疫刺激微环境，其中包含更多的肿瘤浸润淋巴细胞 (TIL) 和炎症特征的上调，预示着抗 PD1 疗法的反应，而与基线相比，治疗结束时残留的肿瘤受到免疫抑制。 NAC 引起的 TIL 和 CD8+ T 细胞比例的增加与病理完全缓解独立相关。此外，治疗中的免疫反应比配对基线样本中的免疫特征更能预测治疗结果，尽管这些特征密切相关。新辅助化疗是治疗乳腺癌的一种治疗选择。在这里，作者描述了新辅助化疗之前、期间和之后进行的一系列乳腺癌活检中基因表达谱和免疫微环境的变化。
To elucidate the effects of neoadjuvant chemotherapy (NAC), we conduct whole transcriptome profiling coupled with histopathology analyses of a longitudinal breast cancer cohort of 146 patients including 110 pairs of serial tumor biopsies collected before treatment, after the first cycle of treatment and at the time of surgery. Here, we show that cytotoxic chemotherapies induce dynamic changes in the tumor immune microenvironment that vary by subtype and pathologic response. Just one cycle of treatment induces an immune stimulatory microenvironment harboring more tumor infiltrating lymphocytes (TILs) and up-regulation of inflammatory signatures predictive of response to anti-PD1 therapies while residual tumors are immune suppressed at end-of-treatment compared to the baseline. Increases in TILs and CD8+ T cell proportions in response to NAC are independently associated with pathologic complete response. Further, on-treatment immune response is more predictive of treatment outcome than immune features in paired baseline samples although these are strongly correlated. Neoadjuvant chemotherapy is a therapeutic option for the treatment of breast cancer. Here, the authors characterize changes in the gene expression profiles and immune microenvironment in serial breast cancer biopsies taken before, during and after neoadjuvant chemotherapy.
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DOI：
10.1158/1078-0432.ccr-11-2762
发表时间：
2012-02-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Gonzalez-Angulo AM;Iwamoto T;Liu S;Chen H;Do KA;Hortobagyi GN;Mills GB;Meric-Bernstam F;Symmans WF;Pusztai L
通讯作者：
Pusztai L
影响因子：
5.8
作者：
Kim, Hyunsoo;Park, Haesun
通讯作者：
Park, Haesun
影响因子：
168.9
作者：
Gianni, Luca;Eiermann, Wolfgang;Baselga, Jose
通讯作者：
Baselga, Jose
影响因子：
11.5
作者：
Bardia, Aditya;Baselga, Jose
通讯作者：
Baselga, Jose
DOI：
10.1158/1078-0432.ccr-14-1760
发表时间：
2015-07-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
DeMichele A;Yee D;Berry DA;Albain KS;Benz CC;Boughey J;Buxton M;Chia SK;Chien AJ;Chui SY;Clark A;Edmiston K;Elias AD;Forero-Torres A;Haddad TC;Haley B;Haluska P;Hylton NM;Isaacs C;Kaplan H;Korde L;Leyland-Jones B;Liu MC;Melisko M;Minton SE;Moulder SL;Nanda R;Olopade OI;Paoloni M;Park JW;Parker BA;Perlmutter J;Petricoin EF;Rugo H;Symmans F;Tripathy D;van't Veer LJ;Viscusi RK;Wallace A;Wolf D;Yau C;Esserman LJ
通讯作者：
Esserman LJ