Heterogeneous Tumor-Immune Microenvironments among Differentially Growing Metastases in an Ovarian Cancer Patient.
Heterogeneous Tumor-Immune Microenvironments among Differentially Growing Metastases in an Ovarian Cancer Patient.
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DOI：
10.1016/j.cell.2017.07.025
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发表时间：
2017-08-24
期刊：
影响因子：
64.5
通讯作者：
Miller ML
中科院分区：
文献类型：
--
作者：
Jiménez-Sánchez A;Memon D;Pourpe S;Veeraraghavan H;Li Y;Vargas HA;Gill MB;Park KJ;Zivanovic O;Konner J;Ricca J;Zamarin D;Walther T;Aghajanian C;Wolchok JD;Sala E;Merghoub T;Snyder A;Miller ML
我们报告了一个特殊的病例，患者患有高级别浆液性卵巢癌，接受了多种化疗方案，谁表现出一些转移性病灶的消退，并伴有其他病变的进展，在无治疗期间。利用免疫基因组学方法，我们发现进展性转移以免疫细胞排斥为特征，而退行性和稳定性转移则被CD8+和CD4+ T细胞浸润，并表现出特异性T细胞亚群的寡克隆扩增。我们还检测了从肿瘤切除后近3年的血液样本中分离细胞后CD8+ T细胞对预测的新表位的反应性。这些发现表明，多个不同的肿瘤免疫微环境共存于单个个体中，这可能部分解释了临床治疗后经常观察到的转移性病变的异质性命运。非治疗期转移的差异进展。不同肿瘤免疫微环境在同一个体内共存。肿瘤的消退和进展与T细胞浸润和排斥相关。克隆性新表位引起循环CD8+ T细胞的反应性。不同的肿瘤免疫微环境共存于单个个体中，可能有助于解释治疗后经常观察到的转移性病变的异质性命运。
We present an exceptional case of a patient with high-grade serous ovarian cancer, treated with multiple chemotherapy regimens, who exhibited regression of some metastatic lesions with concomitant progression of other lesions during a treatment-free period. Using immunogenomic approaches, we found that progressing metastases were characterized by immune cell exclusion, whereas regressing and stable metastases were infiltrated by CD8+ and CD4+ T cells and exhibited oligoclonal expansion of specific T cell subsets. We also detected CD8+ T cell reactivity against predicted neoepitopes after isolation of cells from a blood sample taken almost 3 years after the tumors were resected. These findings suggest that multiple distinct tumor immune microenvironments co-exist within a single individual and may explain in part the heterogeneous fates of metastatic lesions often observed in the clinic post-therapy. Differential progression of metastases during off-treatment period. Coexistence of distinct tumor-immune microenvironments within the same individual. Tumor regression and progression correlated with T cell infiltration and exclusion. Clonal neoepitopes elicited reactivity of circulating CD8+ T cells. Distinct tumor immune microenvironments co-exist within a single individual and may help to explain the heterogeneous fates of metastatic lesions often observed post-therapy.
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影响因子：
--
作者：
Gavalas NG;Karadimou A;Dimopoulos MA;Bamias A
通讯作者：
Bamias A
影响因子：
28.2
作者：
Chen PL;Roh W;Reuben A;Cooper ZA;Spencer CN;Prieto PA;Miller JP;Bassett RL;Gopalakrishnan V;Wani K;De Macedo MP;Austin-Breneman JL;Jiang H;Chang Q;Reddy SM;Chen WS;Tetzlaff MT;Broaddus RJ;Davies MA;Gershenwald JE;Haydu L;Lazar AJ;Patel SP;Hwu P;Hwu WJ;Diab A;Glitza IC;Woodman SE;Vence LM;Wistuba II;Amaria RN;Kwong LN;Prieto V;Davis RE;Ma W;Overwijk WW;Sharpe AH;Hu J;Futreal PA;Blando J;Sharma P;Allison JP;Chin L;Wargo JA
通讯作者：
Wargo JA
影响因子：
64.5
作者：
Benci JL;Xu B;Qiu Y;Wu TJ;Dada H;Twyman-Saint Victor C;Cucolo L;Lee DSM;Pauken KE;Huang AC;Gangadhar TC;Amaravadi RK;Schuchter LM;Feldman MD;Ishwaran H;Vonderheide RH;Maity A;Wherry EJ;Minn AJ
通讯作者：
Minn AJ
影响因子：
7.3
作者：
Bashashati, Ali;Ha, Gavin;Tone, Alicia;Ding, Jiarui;Prentice, Leah M.;Roth, Andrew;Rosner, Jamie;Shumansky, Karey;Kalloger, Steve;Senz, Janine;Yang, Winnie;McConechy, Melissa;Melnyk, Nataliya;Anglesio, Michael;Luk, Margaret T. Y.;Tse, Kane;Zeng, Thomas;Moore, Richard;Zhao, Yongjun;Marra, Marco A.;Gilks, Blake;Yip, Stephen;Huntsman, David G.;McAlpine, Jessica N.;Shah, Sohrab P.
通讯作者：
Shah, Sohrab P.
MHC I类的性质提出了增强免疫原性的肽。
影响因子：
4.3
作者：
Calis JJ;Maybeno M;Greenbaum JA;Weiskopf D;De Silva AD;Sette A;Keşmir C;Peters B
通讯作者：
Peters B