Abstract P3-08-15: Immunologic correlates of long-term outcome in the residual disease of triple-negative breast cancer after neoadjuvant chemotherapy

作者: Justin M Balko , Mellissa Nixon , Paula I Gonzalez-Ericsson , Mark A Pilkinton , Wyatt J McDonnell

DOI: 10.1158/1538-7445.SABCS19-P3-08-15

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摘要: The recent approval of anti-PD-L1 immunotherapy in combination with nAB-paclitaxel for metastatic triple-negative breast cancer (TNBC) highlights the need to understand role chemotherapy modulating tumor-immune microenvironment (TIME). Patients TNBC are routinely treated neoadjuvant (NAC). Stromal tumor-infiltrating lymphocytes (sTILs) pre-treatment diagnostic biopsy predictive pathologic complete response (pCR). In patients residual disease (RD) at surgery, sTILs confer good prognosis. However, effect on and how it influences TIME poorly understood. We examined immune-gene expression patterns before after NAC a series 83 tumors, including 44 TNBCs, from RD. were enumerated by standardized guidelines. Gene tested association recurrence-free (RFS) overall survival (OS). T cell receptor sequencing (TCRseq) was performed subset (n=15) tumors. 4 undergoing NAC, PD-1-high -negative CD8+ peripheral blood mononuclear cells (PBMCs) profiled using single-cell RNAseq multiplexed cytokine secretion assays. Post-NAC (≥30%) only outcome (RFS p=0.019; OS p=0.05) patients, but not non-TNBC p=0.28; p=0.78) confirming that prognostic capacity is confined TNBC. Pre-NAC either group, likely due exclusion experiencing pCR. change during did prognosticate TNBC, suggesting post-NAC setting, most proximal measurement meaningful. these results suggest alters TIME. To examine interplay among TIME, clinical outcomes, we 770 immune-related genes univariate cox-proportional hazards models. non-TNBC, no any single gene associated RFS or false-discovery rate (FDR) 10%. individual changes 12 204 identified as OS, respectively (FDR Citation Format: Justin M Balko, Mellissa Nixon, Paula I Gonzalez-Ericsson, Mark A Pilkinton, Wyatt J McDonnell, Violeta Sanchez, Susan R Opalenik, Sherene Loi, Brent Rexer, Vandana Abramson, Valerie Jansen, Simon Mallal, Jonathan D Marotti, Kevin Shee, Todd W Miller, Melinda E Sanders, Ingrid Mayer, Roberto Salgado. Immunologic correlates long-term [abstract]. In: Proceedings 2019 San Antonio Breast Cancer Symposium; Dec 10-14; Antonio, TX. Philadelphia (PA): AACR; Res 2020;80(4 Suppl):Abstract nr P3-08-15.

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