Immune Phenotype and Response to Neoadjuvant Therapy in Triple-Negative Breast Cancer.
Immune Phenotype and Response to Neoadjuvant Therapy in Triple-Negative Breast Cancer.
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DOI：
10.1158/1078-0432.ccr-21-0144
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发表时间：
2021-10-01
期刊：
影响因子：
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通讯作者：
Mittendorf EA
中科院分区：
文献类型：
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作者：
Yam C;Yen EY;Chang JT;Bassett RL;Alatrash G;Garber H;Huo L;Yang F;Philips AV;Ding QQ;Lim B;Ueno NT;Kannan K;Sun X;Sun B;Parra Cuentas ER;Symmans WF;White JB;Ravenberg E;Seth S;Guerriero JL;Rauch GM;Damodaran S;Litton JK;Wargo JA;Hortobagyi GN;Futreal A;Wistuba II;Sun R;Moulder SL;Mittendorf EA
Increasing tumor-infiltrating lymphocytes (TILs) is associated with higher rates of pathologic complete response (pCR) to neoadjuvant therapy (NAT) in patients with triple-negative breast cancer (TNBC). However, the presence of TILs does not consistently predict pCR, therefore, the current study was undertaken to more fully characterize the immune cell response and its association with pCR. We obtained pre-treatment core needle biopsies from 105 patients with stage I-III TNBC enrolled in ARTEMIS (NCT02276443) who received NAT from 10/22/2015 through 7/24/2018. The tumor-immune microenvironment was comprehensively profiled by performing T-cell receptor (TCR) sequencing, PD-L1 immunohistochemistry, multiplex immunofluorescence and RNA sequencing on pretreatment tumor samples. The primary endpoint was pathological response to NAT. The pCR rate was 40% (42/105). Higher TCR clonality (median=0.2 vs 0.1, p=0.03), PD-L1 positivity (odds ratio: 2.91, p=0.020), higher CD3+:CD68+ ratio (median=14.70 vs 8.20, p=0.0128), and closer spatial proximity of T-cells to tumor cells (median=19.26μm vs 21.94μm, p=0.0169) were associated with pCR. In a multivariable model, the closer spatial proximity of T-cells to tumor cells and PD-L1 expression enhanced prediction of pCR when considered in conjunction with clinical stage. In patients receiving NAT for TNBC, deep immune profiling through detailed phenotypic characterization and spatial analysis can improve prediction of pCR in patients receiving NAT for TNBC when considered with traditional clinical parameters.
