Journal
FRONTIERS IN IMMUNOLOGY
Volume 10, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2019.02802
Keywords
immunotherapy; triple negative breast cancer; chemotherapy treated patients; transcriptomic signature; outcome
Categories
Funding
- Instituto de Salud Carlos III, ACEPAIN [PI16/01121]
- CIBERONC
- CRIS Cancer Foundation
- Ministry of Economy and Competitiveness of Spain [BFU2015-71371-R]
- Instituto de Salud Carlos III through the Spanish Cancer Centers Network Program [RD12/0036/0003]
- Instituto de Salud Carlos III through CIBERONC
- scientific foundation of the AECC
- CRIS Foundation
- European Community through the regional development funding program (FEDER)
- Diputacion de Albacete
- [NVKP_16-1-2016-0037]
- [2018-1.3.1-VKE-2018-00032]
- [KH-129581]
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Limited therapeutic options exist for the treatment of patients with triple negative breast cancer (TNBC). Neoadjuvant chemotherapy is currently the standard of care treatment in the early stages of the disease, although reliable biomarkers of response have been scarcely described. In our study we explored whether immunologic signatures associated with inflamed tumors or hot tumors could predict the outcome to neoadjuvant chemotherapy. Publicly available transcriptomic data of more than 2,000 patients were evaluated. ROC plots were generated to assess the response to therapy. Cox proportional hazards regression was computed. Kaplan-Meier plots were drawn to visualize the survival differences. Higher expression of IDO1, CXCL9, CXCL10, HLA-DRA, HLA-E, STAT1, and GZMB were associated with a higher proportion without relapse in the first 5 y after chemotherapy in TNBC. The expression of these genes was associated with a high presence of CD8 T cells in responder patients using the EPIC bioinformatic tool. The strongest effect was observed for STAT1 (p = 1.8e-05 and AUC 0.69, p = 2.7e-06). The best gene-set signature to predict favorable RFS was the combination of IDO1, LAG3, STAT1, and GZMB (HR = 0.28, CI = 0.17-0.46, p = 9.8 E-08, FDR = 1%). However, no influence on pathological complete response (pCR) was observed. Similarly, no benefit was identified in any other tumor subtype: HER2 or estrogen receptor positive. In conclusion, we describe a set of immunologic genes that predict the outcome to neoadjuvant chemotherapy in TNBC, but not pCR, suggesting that this non-time to event endpoint is not a good surrogate marker to detect the long term outcome for immune activated tumors.
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