PMID- 34489928
OWN - NLM
STAT- MEDLINE
DCOM- 20211020
LR  - 20211020
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 12
DP  - 2021
TI  - Autologous Dendritic Cells in Combination With Chemotherapy Restore 
      Responsiveness of T Cells in Breast Cancer Patients: A Single-Arm Phase I/II 
      Trial.
PG  - 669965
LID - 10.3389/fimmu.2021.669965 [doi]
LID - 669965
AB  - INTRODUCTION: Animal studies and preclinical studies in cancer patients suggest 
      that the induction of immunogenic cell death (ICD) by neoadjuvant chemotherapy 
      with doxorubicin and cyclophosphamide (NAC-AC) recovers the functional 
      performance of the immune system. This could favor immunotherapy schemes such as 
      the administration of antigen-free autologous dendritic cells (DCs) in 
      combination with NAC-AC to profit as cryptic vaccine immunogenicity of treated 
      tumors. OBJECTIVE: To explore the safety and immunogenicity of autologous 
      antigen-free DCs administered to breast cancer patients (BCPs) in combination 
      with NAC-AC. MATERIALS AND METHODS: A phase I/II cohort clinical trial was 
      performed with 20 BCPs treated with NAC-AC [nine who received DCs and 11 who did 
      not (control group)]. The occurrence of adverse effects and the functional 
      performance of lymphocytes from BCPs before and after four cycles of NAC-AC 
      receiving DCs or not were assessed using flow cytometry and compared with that 
      from healthy donors (HDs). Flow cytometry analysis using manual and automated 
      algorithms led us to examine functional performance and frequency of different 
      lymphocyte compartments in response to a stimulus in vitro. This study was 
      registered at clinicaltrials.gov (NCT03450044). RESULTS: No grade II or higher 
      adverse effects were observed associated with the transfer of DCs to patients 
      during NAC-AC. Interestingly, in response to the in vitro stimulation, deficient 
      phosphorylation of Zap70 and AKT proteins observed before chemotherapy in most 
      patients' CD4 T cells significantly recovered after NAC-AC only in patients who 
      received DCs. CONCLUSIONS: The transfer of autologous DCs in combination with 
      NAC-AC in BCPs is a safe procedure. That, in BCPs, the administration of DCs in 
      combination with NAC-AC favors the recovery of the functional capacity of T cells 
      suggests that this combination may potentiate the adjuvant effect of ICD induced 
      by NAC-AC on T cells and, hence, potentiate the immunogenicity of tumors as 
      cryptic vaccines.
CI  - Copyright (c) 2021 Bernal-Estevez, Ortiz Barbosa, Ortiz-Montero, Cifuentes, Sanchez 
      and Parra-Lopez.
FAU - Bernal-Estevez, David A
AU  - Bernal-Estevez DA
AD  - Immunology and Clinical Oncology Research Group, Fundacion Salud de los Andes, 
      Bogota, Colombia.
FAU - Ortiz Barbosa, Mauren A
AU  - Ortiz Barbosa MA
AD  - Immunology and Clinical Oncology Research Group, Fundacion Salud de los Andes, 
      Bogota, Colombia.
FAU - Ortiz-Montero, Paola
AU  - Ortiz-Montero P
AD  - Immunology and Clinical Oncology Research Group, Fundacion Salud de los Andes, 
      Bogota, Colombia.
FAU - Cifuentes, Claudia
AU  - Cifuentes C
AD  - Oncology Department, Hospital Universitario Mayor de Mederi, Bogota, Colombia.
FAU - Sanchez, Ramiro
AU  - Sanchez R
AD  - Immunology and Translational Medicine Research Group, Department of Microbiology, 
      Medical School, Universidad Nacional de Colombia, Bogota, Colombia.
FAU - Parra-Lopez, Carlos A
AU  - Parra-Lopez CA
AD  - Immunology and Translational Medicine Research Group, Department of Microbiology, 
      Medical School, Universidad Nacional de Colombia, Bogota, Colombia.
LA  - eng
SI  - ClinicalTrials.gov/NCT03450044
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20210820
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Cancer Vaccines)
RN  - 80168379AG (Doxorubicin)
RN  - 8N3DW7272P (Cyclophosphamide)
SB  - IM
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use
MH  - Breast Neoplasms/immunology/pathology/*therapy
MH  - Cancer Vaccines/adverse effects/immunology/*therapeutic use
MH  - Chemotherapy, Adjuvant
MH  - Colombia
MH  - Cyclophosphamide/therapeutic use
MH  - Dendritic Cells/immunology/*transplantation
MH  - Doxorubicin/therapeutic use
MH  - Female
MH  - Humans
MH  - *Immunotherapy, Adoptive/adverse effects
MH  - Lymphocytes, Tumor-Infiltrating/*immunology
MH  - Middle Aged
MH  - *Neoadjuvant Therapy
MH  - T-Lymphocytes/*immunology
MH  - Time Factors
MH  - Treatment Outcome
MH  - Tumor Microenvironment
PMC - PMC8417880
OTO - NOTNLM
OT  - breast cancer
OT  - clinical trial
OT  - dendritic cells
OT  - immunotherapy
OT  - neoadjuvant chemotherapy
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/09/08 06:00
MHDA- 2021/10/21 06:00
PMCR- 2021/01/01
CRDT- 2021/09/07 07:43
PHST- 2021/02/19 00:00 [received]
PHST- 2021/07/27 00:00 [accepted]
PHST- 2021/09/07 07:43 [entrez]
PHST- 2021/09/08 06:00 [pubmed]
PHST- 2021/10/21 06:00 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2021.669965 [doi]
PST - epublish
SO  - Front Immunol. 2021 Aug 20;12:669965. doi: 10.3389/fimmu.2021.669965. eCollection 
      2021.