Molecular signatures of circulating melanoma cells for monitoring early response to immune checkpoint therapy

Hong Xin; Sullivan Ryan J.; Kalinich MarkKwan Tanya TodorovaGiobbie-Hurder AnitaPan ShiweiLiCausi Joseph A.Milner John D.Nieman Linda T.Wittner Ben S.Ho UyenChen TianqiKapur RaviLawrence Donald P.Flaherty Keith T.Sequist Lecia V.Ramaswamy SridharMiyamoto David T.Lawrence MichaelToner MehmetIsselbacher Kurt J.Maheswaran ShyamalaHaber Daniel A.

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Molecular signatures of circulating melanoma cells for monitoring early response to immune checkpoint therapy

机译：Molecular signatures of circulating melanoma cells for monitoring early response to immune checkpoint therapy

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A subset of patients with metastatic melanoma have sustained remissions following treatment with immune checkpoint inhibitors. However, analyses of pretreatment tumor biopsies for markers predictive of response, including PD-1 ligand (PD-L1) expression and mutational burden, are insufficiently precise to guide treatment selection, and clinical radiographic evidence of response on therapy may be delayed, leading to some patients receiving potentially ineffective but toxic therapy. Here, we developed a molecular signature of melanoma circulating tumor cells (CTCs) to quantify early tumor response using blood-based monitoring. A quantitative 19-gene digital RNA signature (CTC score) applied to microfluidically enriched CTCs robustly distinguishes melanoma cells, within a background of blood cells in reconstituted and in patient-derived (n = 42) blood specimens. In a prospective cohort of 49 patients treated with immune checkpoint inhibitors, a decrease in CTC score within 7 weeks of therapy correlates with marked improvement in progression-free survival hazard ratio (HR), 0.17; P = 0.008 and overall survival (HR, 0.12; P = 0.04). Thus, digital quantitation of melanoma CTC-derived transcripts enables serial noninvasive monitoring of tumor burden, supporting the rational application of immune checkpoint inhibition therapies.

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《Proceedings of the National Academy of Sciences of the United States of America.》 |2018年第10期|2467-2472|共6页
作者
Hong Xin; Sullivan Ryan J.; Kalinich MarkKwan Tanya TodorovaGiobbie-Hurder AnitaPan ShiweiLiCausi Joseph A.Milner John D.Nieman Linda T.Wittner Ben S.Ho UyenChen TianqiKapur RaviLawrence Donald P.Flaherty Keith T.Sequist Lecia V.Ramaswamy SridharMiyamoto David T.Lawrence MichaelToner MehmetIsselbacher Kurt J.Maheswaran ShyamalaHaber Daniel A.;
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作者单位

Harvard Med Sch, Massachusetts Gen Hosp, Canc Ctr, Boston, MA 02114 USA;

Harvard Med Sch, Massachusetts Gen Hosp, Ctr Bioengn Med, Boston, MA 02114 USA;

Harvard Med Sch, Dana Farber Canc Inst, Div Biostat, Boston, MA 02215 USA;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
circulating tumor cells; liquid biopsy; predictive biomarker; melanoma; immune checkpoint inhibition;

Molecular signatures of circulating melanoma cells for monitoring early response to immune checkpoint therapy

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