Details

Autor(en) / Beteiligte

• Messaoudene, M.
• Mourikis, T.P.
• Michels, J.
• Fu, Y.
• Bonvalet, M.
• Lacroix-Trikki, M.
• Routy, B.
• Fluckiger, A.
• Rusakiewicz, S.
• Roberti, M.P.
• Cotteret, S.
• Flament, C.
• Poirier-Colame, V.
• Jacquelot, N.
• Ghiringhelli, F.
• Caignard, A.
• Eggermont, A.M.M.
• 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.

Titel

T-cell bispecific antibodies in node-positive breast cancer: novel therapeutic avenue for MHC class I loss variants

Ist Teil von

• Annals of oncology, 2019-06, Vol.30 (6), p.934-944

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2019

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. 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. 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. TCB should be developed in BC to circumvent low MHC/peptide complexes.