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Master Thesis

Pronostic de l'infiltrat inflammatoire dans les cancers du sein triple-négatifs (PRINCESSE) : constitution d'une signature transcriptomique pronostique liée à l'inflammation

Abstract : Purpose: triple-negative breast cancer (TNBC) patients have up to 75% risk of metastatic relapse within the following years when they have residual disease (RD) after neo-adjuvant chemotherapy (NACT). The immune infiltrate in TNBC being prognostic and predictive of response to treatment, we sought to develop an immunologic transcriptomic signature to better predict relapse in these patients. Experimental design: We identified 115 samples of residual tumors from post-NACT TNBC patients. We profiled the expression of 770 genes related to cancer microenvironment using the Nanostring PanCancer IO360 panel to develop a prognostic transcriptomic signature, and describe the immune microenvironment of the residual tumor. Results: thirty-eight (33%) of patients experienced metastatic relapse. Hierarchical clustering separated patients into 5 clusters with distinct prognosis, based on pathways linked to immune activation, epithelial to mesenchymal transition and cell cycle. The immune microenvironment of the residual disease was significantly different between patients who experienced relapse compared to those who did not, the latter having significantly more effector anti-tumoral immune cells, with significant differences in lymphoid subpopulations. We selected eight genes linked to immunity (BLK, GZMM, CXCR6, LILRA1, SPIB, CCL4, CXCR4, SLAMF7) to develop a transcriptomic signature which could predict relapse in our cohort and in the RCB2 subgroup. This signature was validated in two external cohorts (KMplot and METABRIC). Conclusions: lack of immune activation after NACT appears to be a strong prognostic factor for metastatic relapse. We propose a prognostic signature based on immune infiltrate that could lead to targeted therapeutic strategies to improve patients’ prognosis.
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https://dumas.ccsd.cnrs.fr/dumas-03376597
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Submitted on : Wednesday, October 13, 2021 - 3:45:54 PM
Last modification on : Tuesday, November 23, 2021 - 3:15:41 AM

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  • HAL Id : dumas-03376597, version 1

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Céline Blaye. Pronostic de l'infiltrat inflammatoire dans les cancers du sein triple-négatifs (PRINCESSE) : constitution d'une signature transcriptomique pronostique liée à l'inflammation. Sciences du Vivant [q-bio]. 2021. ⟨dumas-03376597⟩

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