PMID- 37870457
OWN - NLM
STAT- MEDLINE
DCOM- 20231114
LR  - 20231122
IS  - 2373-9878 (Electronic)
IS  - 2373-9878 (Linking)
VI  - 9
IP  - 11
DP  - 2023 Nov 13
TI  - Tumor Antigen-Primed Dendritic Cell-Derived Exosome Synergizes with Colony 
      Stimulating Factor-1 Receptor Inhibitor by Modulating the Tumor Microenvironment 
      and Systemic Immunity.
PG  - 6409-6424
LID - 10.1021/acsbiomaterials.3c00469 [doi]
AB  - Dendritic cell-derived exosomes (Dex) have overcome the disadvantages associated 
      with dendritic cell (DC) vaccines, such as cost effectiveness, stability, and 
      sensitivity to the systemic microenvironment. However, in clinical trials, Dex 
      failed to provide satisfactory results because of many reasons, including 
      inadequate maturation of DC as well as the immunosuppressive tumor 
      microenvironment (TME). Hence, culturing DCs in the presence of a maturation 
      cocktail showed an induced expression of MHCs and co-stimulatory molecules. 
      Additionally, targeting the colony stimulating factor-1 (CSF-1)/CSF-1 receptor 
      (CSF-1R) signaling pathway by a CSF-1R inhibitor could deplete tumor-associated 
      macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) which are 
      responsible for immunosuppressive TME. Hence, in this study, mDex(TA) were 
      isolated from bone marrow-derived DC cultured in the presence of a novel 
      maturation cocktail and tumor antigen. mDex(TA) showed elevated expression of 
      major histocompatibility complexes (MHCs) and co-stimulatory molecules and was 
      found capable of activating naive DC and T cells in vitro more efficiently when 
      compared to imDex(TA) isolated from immature DCs. In addition, PLX-3397, a small 
      molecule inhibitor of CSF-1/CSF-1R, was used in combination to enhance the 
      antitumor efficacy of mDex(TA). PLX-3397 showed dose-dependent toxicity against 
      bone marrow-derived macrophages (BMDMs). In the B16-F10 murine melanoma model, we 
      found that the combination treatment delayed tumor growth and improved survival 
      compared to the mice treated with mDex(TA) alone by enhancing the CD8 T cells 
      infiltration in TME. mDex(TA) when combined with PLX-3397 modulated the TME by 
      shifting the Th1/Th2 toward a dominant Th1 population and depleting the TAMs and 
      MDSCs. Interestingly, PLX-3397-induced FoxP3 expression was diminished when it 
      was used in combination with mDex(TA). Combination treatment also induced 
      favorable systemic antitumor immunity in the spleen and lymph node. In 
      conclusion, our findings provide insights into the synergy between mDex(TA)-based 
      immunotherapy and PLX-3397 as the combination overcame the disadvantages 
      associated with monotherapy and offer a therapeutic strategy for the treatment of 
      solid tumors including melanoma.
FAU - Barnwal, Anjali
AU  - Barnwal A
AD  - Centre for Biomedical Engineering, Indian Institute of Technology Delhi, New 
      Delhi 110016, India.
AD  - Department of Biomedical Engineering, All India Institute of Medical Science, 
      Delhi 110029, India.
FAU - Gaur, Vidit
AU  - Gaur V
AD  - Centre for Biomedical Engineering, Indian Institute of Technology Delhi, New 
      Delhi 110016, India.
AD  - Department of Biomedical Engineering, All India Institute of Medical Science, 
      Delhi 110029, India.
FAU - Sengupta, Anindita
AU  - Sengupta A
AD  - Centre for Biomedical Engineering, Indian Institute of Technology Delhi, New 
      Delhi 110016, India.
AD  - Department of Biomedical Engineering, All India Institute of Medical Science, 
      Delhi 110029, India.
FAU - Tyagi, Witty
AU  - Tyagi W
AUID- ORCID: 0000-0002-6164-3523
AD  - National Institute of Immunology, Delhi 110067, India.
FAU - Das, Sanjeev
AU  - Das S
AD  - National Institute of Immunology, Delhi 110067, India.
FAU - Bhattacharyya, Jayanta
AU  - Bhattacharyya J
AUID- ORCID: 0000-0003-0202-4770
AD  - Centre for Biomedical Engineering, Indian Institute of Technology Delhi, New 
      Delhi 110016, India.
AD  - Department of Biomedical Engineering, All India Institute of Medical Science, 
      Delhi 110029, India.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20231023
PL  - United States
TA  - ACS Biomater Sci Eng
JT  - ACS biomaterials science & engineering
JID - 101654670
RN  - 81627-83-0 (Macrophage Colony-Stimulating Factor)
RN  - 0 (Antigens, Neoplasm)
SB  - IM
MH  - Mice
MH  - Animals
MH  - Macrophage Colony-Stimulating Factor/pharmacology
MH  - Tumor Microenvironment
MH  - *Exosomes
MH  - Antigens, Neoplasm
MH  - *Melanoma
MH  - Dendritic Cells
OTO - NOTNLM
OT  - CSF-1R inhibitor
OT  - Cancer immunotherapy
OT  - DC-derived exosomes
OT  - Melanoma
OT  - PLX-3397
OT  - Tumor microenvironment
EDAT- 2023/10/23 12:42
MHDA- 2023/11/14 06:43
CRDT- 2023/10/23 10:03
PHST- 2023/11/14 06:43 [medline]
PHST- 2023/10/23 12:42 [pubmed]
PHST- 2023/10/23 10:03 [entrez]
AID - 10.1021/acsbiomaterials.3c00469 [doi]
PST - ppublish
SO  - ACS Biomater Sci Eng. 2023 Nov 13;9(11):6409-6424. doi: 
      10.1021/acsbiomaterials.3c00469. Epub 2023 Oct 23.