PMID- 30106435
OWN - NLM
STAT- MEDLINE
DCOM- 20181115
LR  - 20181115
IS  - 1791-2431 (Electronic)
IS  - 1021-335X (Linking)
VI  - 40
IP  - 4
DP  - 2018 Oct
TI  - Sonodynamic therapy improves anti‑tumor immune effect by increasing the 
      infiltration of CD8+ T cells and altering tumor blood vessels in murine B16F10 
      melanoma xenograft.
PG  - 2163-2170
LID - 10.3892/or.2018.6612 [doi]
AB  - Sonodynamic therapy (SDT) uses a combination of sonosensitizers and low‑intensity 
      therapeutic ultrasound to destroy tumor cells. However, its effects on the tumor 
      microenvironment, particularly on the immune state, remain unknown. The purpose 
      of the present study was to examine the capacity and potency of the antitumor 
      immunity induced by SDT. In the present study, sonosensitizer, 5‑aminolevulinic 
      acid (5‑ALA), and/or ultrasound (US) were used to treat mouse B16F10 melanoma 
      xenograft (1.0 MHz, 0.8 W/cm2, 10% duty cycle) and human umbilical vein 
      endothelial cells (HUVECs; 0.87 MHz, 0.6 W/cm2, 60% duty cycle). Various immune 
      cells, and proteins associated with the immunoregulation such as forkhead Box P3 
      (Foxp3), cytotoxic T‑lymphocyte associated protein 4 (CTLA‑4), and CD80 were 
      detected by immunofluorescence staining and western blotting. The effect of SDT 
      on blood vessels which were located in the central and peripheral area of tumor 
      tissues was observed by transmission electron microscopy, immunohistochemical and 
      immunofluorescence staining. The effect of SDT on intercellular adhesion 
      molecule‑1 (ICAM‑1) expression on HUVECs was detected by western blotting and 
      reverse transcription‑semi‑quantitative polymerase chain reaction. The results 
      revealed that SDT inhibited tumor growth and improved outcomes. The mean 
      inhibition rate of tumor volume in the US + ALA group was 43.8% and median 
      survival was 45 days in US + ALA group vs. 27.5 days in the control group. SDT 
      increased the number of CD45+ cells, in particular CD8+ and CD68+ cells and 
      upregulated the expression of CD80 in the tumor tissues. The expression levels of 
      Foxp3 and CTLA‑4 were downregulated following SDT. The endothelial cells of tumor 
      central were damaged, but the lumen area of the tumor peripheral vessels (TPVs) 
      and the expression of ICAM‑1 on HUVECs were increased after SDT. The results 
      indicated that SDT improved the outcomes of melanoma‑loading mice, increased the 
      infiltration of CD8+ T cells and downregulates the expression of Foxp3 and CTLA‑4 
      in mouse melanoma tissues. Furthermore, SDT increased the lumen area of TPVs in 
      murine xenograft and the expression of ICAM‑1 on HUVECs, which may be beneficial 
      to the transendothelial migration of immune cells and the anti‑tumor immune 
      response.
FAU - Peng, Yan
AU  - Peng Y
AD  - Department of Anatomy, Basic Medical Science College, Harbin Medical University, 
      Harbin, Heilongjiang 150081, P.R. China.
FAU - Jia, Limin
AU  - Jia L
AD  - Department of Anatomy, Basic Medical Science College, Harbin Medical University, 
      Harbin, Heilongjiang 150081, P.R. China.
FAU - Wang, Shan
AU  - Wang S
AD  - Department of Oral Pathology, Stomatological Hospital, Harbin Medical University, 
      Harbin, Heilongjiang 150001, P.R. China.
FAU - Cao, Wenwu
AU  - Cao W
AD  - Condensed Matter Science and Technology Institute, and Department of Physics, 
      Harbin Institute of Technology, Harbin, Heilongjiang 150080, P.R. China.
FAU - Zheng, Jinhua
AU  - Zheng J
AD  - Department of Anatomy, Basic Medical Science College, Harbin Medical University, 
      Harbin, Heilongjiang 150081, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20180801
PL  - Greece
TA  - Oncol Rep
JT  - Oncology reports
JID - 9422756
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (CTLA-4 Antigen)
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (Foxp3 protein, mouse)
RN  - 0 (ICAM1 protein, human)
RN  - 0 (Photosensitizing Agents)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 88755TAZ87 (Aminolevulinic Acid)
SB  - IM
MH  - Aminolevulinic Acid/pharmacology
MH  - Animals
MH  - Apoptosis
MH  - Biomarkers, Tumor/*metabolism
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - CTLA-4 Antigen/metabolism
MH  - Cell Proliferation
MH  - Combined Modality Therapy
MH  - Forkhead Transcription Factors/metabolism
MH  - Human Umbilical Vein Endothelial Cells/*immunology
MH  - Humans
MH  - Intercellular Adhesion Molecule-1/metabolism
MH  - Male
MH  - Melanoma, Experimental/blood supply/*immunology/pathology/*therapy
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Neovascularization, Pathologic/immunology/pathology/*therapy
MH  - Photosensitizing Agents/pharmacology
MH  - Tumor Cells, Cultured
MH  - *Ultrasonic Therapy
MH  - Xenograft Model Antitumor Assays
EDAT- 2018/08/15 06:00
MHDA- 2018/11/16 06:00
CRDT- 2018/08/15 06:00
PHST- 2018/01/30 00:00 [received]
PHST- 2018/07/19 00:00 [accepted]
PHST- 2018/08/15 06:00 [pubmed]
PHST- 2018/11/16 06:00 [medline]
PHST- 2018/08/15 06:00 [entrez]
AID - 10.3892/or.2018.6612 [doi]
PST - ppublish
SO  - Oncol Rep. 2018 Oct;40(4):2163-2170. doi: 10.3892/or.2018.6612. Epub 2018 Aug 1.