PMID- 30924846
OWN - NLM
STAT- MEDLINE
DCOM- 20200806
LR  - 20240210
IS  - 1569-8041 (Electronic)
IS  - 0923-7534 (Print)
IS  - 0923-7534 (Linking)
VI  - 30
IP  - 6
DP  - 2019 Jun 1
TI  - T-cell bispecific antibodies in node-positive breast cancer: novel therapeutic 
      avenue for MHC class I loss variants.
PG  - 934-944
LID - S0923-7534(19)31205-0 [pii]
LID - 10.1093/annonc/mdz112 [doi]
AB  - 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 CD3epsilon 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 CD3epsilon 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.
CI  - (c) The Author(s) 2019. Published by Oxford University Press on behalf of the 
      European Society for Medical Oncology. All rights reserved. For permissions, 
      please email: journals.permissions@oup.com.
FAU - Messaoudene, M
AU  - Messaoudene M
AD  - Gustave Roussy Cancer Campus (GRCC), Villejuif; National Institute of Health and 
      Medical Research (INSERM) U1015, Villejuif, France.
FAU - Mourikis, T P
AU  - Mourikis TP
AD  - Cancer Research UK Lung Cancer Centre of Excellence, University College London 
      Cancer Institute, London, UK.
FAU - Michels, J
AU  - Michels J
AD  - Gustave Roussy Cancer Campus (GRCC), Villejuif; University Paris-Sud, University 
      Paris-Saclay, Gustave Roussy Cancer Campus (GRCC), Villejuif; Department of 
      Medical Oncology, Gustave Roussy, Villejuif.
FAU - Fu, Y
AU  - Fu Y
AD  - Gustave Roussy Cancer Campus (GRCC), Villejuif.
FAU - Bonvalet, M
AU  - Bonvalet M
AD  - Gustave Roussy Cancer Campus (GRCC), Villejuif; National Institute of Health and 
      Medical Research (INSERM) U1015, Villejuif, France.
FAU - Lacroix-Trikki, M
AU  - Lacroix-Trikki M
AD  - Gustave Roussy Cancer Campus (GRCC), Villejuif; Center of Clinical Investigations 
      in Biotherapies of Cancer (CICBT) 1428, Villejuif, France.
FAU - Routy, B
AU  - Routy B
AD  - Gustave Roussy Cancer Campus (GRCC), Villejuif; Universitede Montreal Hospital 
      Research Centre (CRCHUM), Onco-Hematology Department, Montreal University 
      Hospital Center (CHUM), Montreal, Quebec, Canada.
FAU - Fluckiger, A
AU  - Fluckiger A
AD  - Gustave Roussy Cancer Campus (GRCC), Villejuif; National Institute of Health and 
      Medical Research (INSERM) U1015, Villejuif, France; Center of Clinical 
      Investigations in Biotherapies of Cancer (CICBT) 1428, Villejuif, France.
FAU - Rusakiewicz, S
AU  - Rusakiewicz S
AD  - Center of Experimental Therapeutics (CET), Department of Oncology, Lausanne 
      University Hospital, CHUV, Lausanne, Switzerland.
FAU - Roberti, M P
AU  - Roberti MP
AD  - Gustave Roussy Cancer Campus (GRCC), Villejuif; National Institute of Health and 
      Medical Research (INSERM) U1015, Villejuif, France; Center of Clinical 
      Investigations in Biotherapies of Cancer (CICBT) 1428, Villejuif, France.
FAU - Cotteret, S
AU  - Cotteret S
AD  - Gustave Roussy Cancer Campus (GRCC), Villejuif.
FAU - Flament, C
AU  - Flament C
AD  - Gustave Roussy Cancer Campus (GRCC), Villejuif; National Institute of Health and 
      Medical Research (INSERM) U1015, Villejuif, France; Center of Clinical 
      Investigations in Biotherapies of Cancer (CICBT) 1428, Villejuif, France.
FAU - Poirier-Colame, V
AU  - Poirier-Colame V
AD  - Gustave Roussy Cancer Campus (GRCC), Villejuif; National Institute of Health and 
      Medical Research (INSERM) U1015, Villejuif, France; Center of Clinical 
      Investigations in Biotherapies of Cancer (CICBT) 1428, Villejuif, France.
FAU - Jacquelot, N
AU  - Jacquelot N
AD  - Gustave Roussy Cancer Campus (GRCC), Villejuif; National Institute of Health and 
      Medical Research (INSERM) U1015, Villejuif, France; University Paris-Sud, 
      University Paris-Saclay, Gustave Roussy Cancer Campus (GRCC), Villejuif.
FAU - Ghiringhelli, F
AU  - Ghiringhelli F
AD  - Georges-Francois Leclerc center, Medical Oncology, Dijon.
FAU - Caignard, A
AU  - Caignard A
AD  - INSERM U1160, University Institute for Haematology, Saint Louis hospital, Paris.
FAU - Eggermont, A M M
AU  - Eggermont AMM
AD  - Gustave Roussy Cancer Campus (GRCC), Villejuif.
FAU - Kroemer, G
AU  - Kroemer G
AD  - Gustave Roussy Cancer Campus (GRCC), Villejuif; University Paris-Sud, University 
      Paris-Saclay, Gustave Roussy Cancer Campus (GRCC), Villejuif; Cell Biology and 
      Metabolomics Platforms, Gustave Roussy Cancer Campus, Cordeliers Research Center, 
      INSERM, U1138, Universite Paris Descartes, Sorbonne Paris Cite; Universite Pierre 
      et Marie Curie; Pole de Biologie, Europeen Georges Pompidou Hospital, AP-HP, 
      Paris.
FAU - Marabelle, A
AU  - Marabelle A
AD  - Gustave Roussy Cancer Campus (GRCC), Villejuif; National Institute of Health and 
      Medical Research (INSERM) U1015, Villejuif, France; University Paris-Sud, 
      University Paris-Saclay, Gustave Roussy Cancer Campus (GRCC), Villejuif; Gustave 
      Roussy Cancer Campus (GRCC), Drug Development Department (DITEP), Villejuif.
FAU - Arnedos, M
AU  - Arnedos M
AD  - Gustave Roussy Cancer Campus (GRCC), Villejuif; Department of Medical Oncology, 
      Gustave Roussy, Villejuif.
FAU - Vicier, C
AU  - Vicier C
AD  - Gustave Roussy Cancer Campus (GRCC), INSERM U981, Villejuif, France.
FAU - Dogan, S
AU  - Dogan S
AD  - Gustave Roussy Cancer Campus (GRCC), Villejuif; Department of Medical Oncology, 
      Gustave Roussy, Villejuif; Gustave Roussy Cancer Campus (GRCC), INSERM U981, 
      Villejuif, France.
FAU - Jaulin, F
AU  - Jaulin F
AD  - Gustave Roussy Cancer Campus (GRCC), Villejuif; Department of Medical Oncology, 
      Gustave Roussy, Villejuif; Gustave Roussy Cancer Campus (GRCC), INSERM U981, 
      Villejuif, France.
FAU - Sammut, S-J
AU  - Sammut SJ
AD  - Cancer Research UK Cambridge Institute and Department of Oncology, University of 
      Cambridge, Cambridge.
FAU - Cope, W
AU  - Cope W
AD  - Cancer Research UK Cambridge Institute and Department of Oncology, University of 
      Cambridge, Cambridge; Cancer Research UK Cancer Centre and National Institute for 
      Health Research Cambridge Biomedical Research Centre, Cambridge University 
      Hospitals NHS Foundation Trust, Cambridge, UK.
FAU - Caldas, C
AU  - Caldas C
AD  - Cancer Research UK Cambridge Institute and Department of Oncology, University of 
      Cambridge, Cambridge.
FAU - Delaloge, S
AU  - Delaloge S
AD  - Gustave Roussy Cancer Campus (GRCC), Villejuif; Department of Medical Oncology, 
      Gustave Roussy, Villejuif.
FAU - McGranahan, N
AU  - McGranahan N
AD  - Cancer Research UK Lung Cancer Centre of Excellence, University College London 
      Cancer Institute, London, UK.
FAU - Andre, F
AU  - Andre F
AD  - Gustave Roussy Cancer Campus (GRCC), Villejuif; Department of Medical Oncology, 
      Gustave Roussy, Villejuif; Gustave Roussy Cancer Campus (GRCC), INSERM U981, 
      Villejuif, France.
FAU - Zitvogel, L
AU  - Zitvogel L
AD  - Gustave Roussy Cancer Campus (GRCC), Villejuif; National Institute of Health and 
      Medical Research (INSERM) U1015, Villejuif, France; University Paris-Sud, 
      University Paris-Saclay, Gustave Roussy Cancer Campus (GRCC), Villejuif; Center 
      of Clinical Investigations in Biotherapies of Cancer (CICBT) 1428, Villejuif, 
      France. Electronic address: Laurence.ZITVOGEL@gustaveroussy.fr.
LA  - eng
GR  - 16942/CRUK_/Cancer Research UK/United Kingdom
GR  - 211179/WT_/Wellcome Trust/United Kingdom
GR  - 211179/Z/18/Z/WT_/Wellcome Trust/United Kingdom
GR  - 23896/CRUK_/Cancer Research UK/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Ann Oncol
JT  - Annals of oncology : official journal of the European Society for Medical 
      Oncology
JID - 9007735
RN  - 0 (Antibodies, Bispecific)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
CIN - Ann Oncol. 2019 Jun 1;30(6):877-879. PMID: 30938431
MH  - Antibodies, Bispecific/*administration & dosage/*immunology
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - Biomarkers, Tumor/metabolism
MH  - Breast Neoplasms/genetics/*immunology/pathology/*therapy
MH  - Female
MH  - Follow-Up Studies
MH  - Genetic Variation
MH  - Histocompatibility Antigens Class I/*genetics/immunology
MH  - Humans
MH  - Lymph Nodes/immunology/pathology
MH  - Lymphatic Metastasis
MH  - Lymphocytes, Tumor-Infiltrating/*immunology
MH  - Neoadjuvant Therapy
MH  - Neoplasm Invasiveness
MH  - Prognosis
MH  - Prospective Studies
MH  - Receptor, ErbB-2/metabolism
PMC - PMC7614969
MID - EMS185035
OTO - NOTNLM
OT  - CEACAM5
OT  - HER2
OT  - HLA loss
OT  - T-cell bispecific antibodies (TCB)
OT  - breast cancer
OT  - tumor-infiltrating lymphocytes (TILs)
COIS- Competing interests. The authors declare no competing interests.
EDAT- 2019/03/30 06:00
MHDA- 2020/08/07 06:00
PMCR- 2023/08/22
CRDT- 2019/03/30 06:00
PHST- 2019/03/30 06:00 [pubmed]
PHST- 2020/08/07 06:00 [medline]
PHST- 2019/03/30 06:00 [entrez]
PHST- 2023/08/22 00:00 [pmc-release]
AID - S0923-7534(19)31205-0 [pii]
AID - 10.1093/annonc/mdz112 [doi]
PST - ppublish
SO  - Ann Oncol. 2019 Jun 1;30(6):934-944. doi: 10.1093/annonc/mdz112.