T-cell bispecific antibodies in node-positive breast cancer: novel therapeutic avenue for MHC class I loss variants.
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Embargo End Date
ICR Authors
Authors
Messaoudene, M
Mourikis, TP
Michels, J
Fu, Y
Bonvalet, M
Lacroix-Trikki, M
Routy, B
Fluckiger, A
Rusakiewicz, S
Roberti, MP
Cotteret, S
Flament, C
Poirier-Colame, V
Jacquelot, N
Ghiringhelli, F
Caignard, A
Eggermont, AMM
Kroemer, G
Marabelle, A
Arnedos, M
Vicier, C
Dogan, S
Jaulin, F
Sammut, S-J
Cope, W
Caldas, C
Delaloge, S
McGranahan, N
André, F
Zitvogel, L
Mourikis, TP
Michels, J
Fu, Y
Bonvalet, M
Lacroix-Trikki, M
Routy, B
Fluckiger, A
Rusakiewicz, S
Roberti, MP
Cotteret, S
Flament, C
Poirier-Colame, V
Jacquelot, N
Ghiringhelli, F
Caignard, A
Eggermont, AMM
Kroemer, G
Marabelle, A
Arnedos, M
Vicier, C
Dogan, S
Jaulin, F
Sammut, S-J
Cope, W
Caldas, C
Delaloge, S
McGranahan, N
André, F
Zitvogel, L
Document Type
Journal Article
Date
2019-06-01
Date Accepted
Abstract
BACKGROUND: Tumor-infiltrating lymphocytes (TILs) represent a prognostic factor for survival in primary breast cancer (BC). Nonetheless, neoepitope load and TILs cytolytic activity are modest in BC, compromising the efficacy of immune-activating antibodies, which do not yet compete against immunogenic chemotherapy. PATIENTS AND METHODS: We analyzed by functional flow cytometry the immune dynamics of primary and metastatic axillary nodes [metastatic lymph nodes (mLN)] in early BC (EBC) after exposure to T-cell bispecific antibodies (TCB) bridging CD3ε and human epidermal growth factor receptor 2 (HER2) or Carcinoembryonic Antigen-Related Cell Adhesion Molecule 5 (CEACAM5), before and after chemotherapy. Human leukocyte antigen (HLA) class I loss was assessed by whole exome sequencing and immunohistochemistry. One hundred primary BC, 64 surrounding 'healthy tissue' and 24 mLN-related parameters were analyzed. RESULTS: HLA loss of heterozygosity was observed in EBC, at a clonal and subclonal level and was associated with regulatory T cells and T-cell immunoglobulin and mucin-domain-3 expression restraining the immuno-stimulatory effects of neoadjuvant chemotherapy. TCB bridging CD3ε and HER2 or CEACAM5 could bypass major histocompatibility complex (MHC) class I loss, partially rescuing T-cell functions in mLN. CONCLUSION: TCB should be developed in BC to circumvent low MHC/peptide complexes.
Citation
Annals of Oncology, 2019, 30 (6), pp. 934 - 944
Source Title
Annals of Oncology
Publisher
ELSEVIER
ISSN
0923-7534
eISSN
1569-8041
Collections
Research Team
Cancer Dynamics