Immune landscape of inflammatory breast cancer suggests vulnerability to immune checkpoint inhibitors

OncoImmunology

Patrice Viens¹  Peter Van Dam²  Christophe Van Berckelaer²  Steven Van Laere²  Luc Dirix³  Naoto T. Ueno⁴  Pascal Finetti⁵  Emilie Mamessier⁵  Anthony Gonçalves⁵  Daniel Birnbaum⁵  François Bertucci⁵  Laurys Boudin⁵ 

[1] CRCM, Institut Paoli-Calmettes;Center for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), University of Antwerp;GZA Hospitals & CORE, MIPRO, University of Antwerp;the University of Texas MD Anderson Cancer Center;“Equipe Labellisée Ligue Contre Le Cancer”, Centre De Recherche En Cancérologie De Marseille (CRCM), Institut Paoli-Calmettes, INSERM UMR1068, CNRS UMR725, Aix-Marseille Université;

关键词: checkpoints;    inflammatory breast cancer;    immune profile;    immunotherapy;    immune checkpoint inhibitors;   

DOI  :  10.1080/2162402X.2021.1929724

来源: DOAJ

【 摘 要 】

Background. Anti-PD1/PDL1 immune checkpoint inhibitors (ICIs) showed promising results in breast cancer, and exploration of additional actionable immune checkpoints is ongoing. Inflammatory breast cancer (IBC) is an aggressive form of disease, the immune tumor microenvironment (TME) of which is poorly known. We aimed at providing the first comprehensive immune portrait of IBCs. Methods. From the gene expression profiles of 137 IBC and 252 non-IBC clinical samples, we measured the fractions of 22 immune cell types, expression of signatures associated with tertiary lymphoid structures (TLS) and with the response to ICIs (T cell-inflamed signature: TIS) and of 18 genes coding for major actionable immune checkpoints. The IBC/non-IBC comparison was adjusted upon the clinicopathological variables. Results. The immune profiles of IBCs were heterogeneous. CIBERSORT analysis showed profiles rich in macrophages, CD8+ and CD4 + T-cells, with remarkable similarity with melanoma TME. The comparison with non-IBCs showed significant enrichment in M1 macrophages, γδ T-cells, and memory B-cells. IBCs showed higher expression of TLS and TIS signatures. The TIS signature displayed values in IBCs close to those observed in other cancers sensitive to ICIs. Two-thirds of actionable immune genes (HAVCR2/TIM3, CD27, CD70, CTLA4, ICOS, IDO1, LAG3, PDCD1, TNFRSF9, PVRIG, CD274/PDL1, and TIGIT) were overexpressed in IBCs as compared to normal breast and two-thirds were overexpressed in IBCs versus non-IBCs, with very frequent co-overexpression. For most of them, the overexpression was associated with better pathological response to chemotherapy. Conclusion. Our results suggest the potential higher vulnerability of IBC to ICIs. Clinical trials.

【 授权许可】

Unknown