PMID- 33908712
OWN - NLM
STAT- MEDLINE
DCOM- 20211022
LR  - 20211022
IS  - 2005-0399 (Electronic)
IS  - 2005-0380 (Print)
IS  - 2005-0380 (Linking)
VI  - 32
IP  - 4
DP  - 2021 Jul
TI  - Autologous cervical tumor lysate pulsed dendritic cell stimulation followed by 
      cisplatin treatment abrogates FOXP3+ cells in vitro.
PG  - e59
LID - 10.3802/jgo.2021.32.e59 [doi]
LID - e59
AB  - OBJECTIVE: Dendritic cells (DCs) are administered as immunotherapeutic adjuvants 
      after the completion of standard treatment in most settings. However, our Phase I 
      trial indicated that one patient out of four, who received autologous tumor 
      lysate-pulsed dendritic cell (TLDC) also received cisplatin chemotherapy and 
      experienced complete regression of her lung lesion, continuing to be disease free 
      till date. Hence, the objective of our current study is to evaluate the 
      sustenance or augmentation of immune responses when autologous human 
      papillomavirus positive cervical tumor lysate pulsed DC- are combined with 
      cisplatin, using co-culture assays in vitro. METHODS: Before treatment, 
      peripheral blood and punch biopsy samples were collected from 23 cervical cancer 
      patients after obtaining an informed consent. DC functionality was confirmed 
      through phenotypic and functional assays using autologous peripheral blood 
      mononuclear cells as responders. For cisplatin experiments, the drug was added at 
      150, 200 (clinical dose equivalent), and 400 muM concentrations to DCs alone or 
      DC-T cell co-cultures. Phenotypic assessment and functional characterization of 
      DCs was done using flow cytometry. Cytokine enzyme-linked immunosorbent assay and 
      interferon (IFN)-gamma enzyme-linked immune absorbent spot assays were also 
      performed. RESULTS: The functionality of TLDCs was not compromised upon cisplatin 
      treatment in vitro even at the highest (400 muM) concentration. Even though 
      cisplatin treatment reduced the secretion of IFN-gamma and interleukin (IL)-12p40 in 
      co-cultures stimulated with TLDCs, this effect was not significant (p>0.05). A 
      doubling of IFN-gamma secretion following cisplatin treatment was observed in at 
      least one of three independent experiments. Additional experiments showed a 
      reduction in both FOXP3+ regulatory T cells and IL-10 levels. CONCLUSION: Our 
      results provide evidence that cisplatin treatment may be given after autologous 
      TLDC administration to maintain or improve a productive anti-tumor response in 
      vaccinated patients.
CI  - Copyright (c) 2021. Asian Society of Gynecologic Oncology, Korean Society of 
      Gynecologic Oncology, and Japan Society of Gynecologic Oncology.
FAU - Dhandapani, Hemavathi
AU  - Dhandapani H
AUID- ORCID: 0000-0002-8103-408X
AD  - Department of Molecular Oncology, Cancer Institute (WIA), Dr. Krishnamurthy 
      Campus, Chennai 600036, India.
FAU - Seetharaman, Abirami
AU  - Seetharaman A
AUID- ORCID: 0000-0002-2981-1726
AD  - Department of Molecular Oncology, Cancer Institute (WIA), Dr. Krishnamurthy 
      Campus, Chennai 600036, India.
FAU - Jayakumar, Hascitha
AU  - Jayakumar H
AUID- ORCID: 0000-0002-5075-1318
AD  - Department of Molecular Oncology, Cancer Institute (WIA), Dr. Krishnamurthy 
      Campus, Chennai 600036, India.
FAU - Ganeshrajah, Selvaluxmy
AU  - Ganeshrajah S
AUID- ORCID: 0000-0002-3722-2331
AD  - Department of Radiation Oncology, Cancer Institute (WIA), Dr. Krishnamurthy 
      Campus, Chennai 600036, India.
FAU - Singh, Shirley Sunder
AU  - Singh SS
AUID- ORCID: 0000-0001-9625-7107
AD  - Department of Oncopathology, Cancer Institute (WIA), Dr. Krishnamurthy Campus, 
      Chennai 600036, India.
FAU - Thangarajan, Rajkumar
AU  - Thangarajan R
AUID- ORCID: 0000-0003-0283-5346
AD  - Department of Molecular Oncology, Cancer Institute (WIA), Dr. Krishnamurthy 
      Campus, Chennai 600036, India.
FAU - Ramanathan, Priya
AU  - Ramanathan P
AUID- ORCID: 0000-0001-8722-3204
AD  - Department of Molecular Oncology, Cancer Institute (WIA), Dr. Krishnamurthy 
      Campus, Chennai 600036, India. priya.serkin@gmail.com.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
DEP - 20210406
PL  - Korea (South)
TA  - J Gynecol Oncol
JT  - Journal of gynecologic oncology
JID - 101483150
RN  - 0 (FOXP3 protein, human)
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (Pharmaceutical Preparations)
RN  - 82115-62-6 (Interferon-gamma)
RN  - Q20Q21Q62J (Cisplatin)
SB  - IM
MH  - Cisplatin
MH  - Dendritic Cells
MH  - Female
MH  - Forkhead Transcription Factors
MH  - Humans
MH  - Interferon-gamma
MH  - Leukocytes, Mononuclear
MH  - *Pharmaceutical Preparations
MH  - *Uterine Cervical Neoplasms/therapy
PMC - PMC8192235
OTO - NOTNLM
OT  - Cervical Cancer
OT  - Chemotherapy, Adjuvant
OT  - Cisplatin
OT  - Dendritic Cells
OT  - Interferon-gamma
OT  - Th1 Cells
COIS- No potential conflict of interest relevant to this article was reported.
EDAT- 2021/04/29 06:00
MHDA- 2023/02/25 06:00
PMCR- 2021/07/01
CRDT- 2021/04/28 09:03
PHST- 2020/10/16 00:00 [received]
PHST- 2021/02/08 00:00 [revised]
PHST- 2021/03/13 00:00 [accepted]
PHST- 2021/04/29 06:00 [pubmed]
PHST- 2023/02/25 06:00 [medline]
PHST- 2021/04/28 09:03 [entrez]
PHST- 2021/07/01 00:00 [pmc-release]
AID - 32.e59 [pii]
AID - 10.3802/jgo.2021.32.e59 [doi]
PST - ppublish
SO  - J Gynecol Oncol. 2021 Jul;32(4):e59. doi: 10.3802/jgo.2021.32.e59. Epub 2021 Apr 
      6.