Shikonin-enhanced cell immunogenicity of tumor vaccine is mediated by the differential effects of DAMP components

Tien-Jen Lin, Hsin Ting Lin, Wei Ting Chang, S. Pradeep Mitapalli, Pei Wen Hsiao, Shu Yi Yin, Ning Sun Yang

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Background: The tumor cell lysate-pulsed, dendritic cell (DC)-based cancer vaccine approaches are being actively evaluated for application to cancer immunotherapy, hopefully at a personalized medicine base. There is apparently an emerging technical problem however, the lack of highly efficacious potency in activation of patient's DCs for T-cell priming and the associated process for presenting tumor immunogenicity. Methods: One strategy to address this is to consider the manipulation of the tumor immunogenic cells death (ICD) complex ex-vivo for maximal activation of DC efficacy. In our previous study we showed that phytochemical shikonin (SK) can drastically enhance ICD activity in mouse tumor cells treated ex-vivo, and the resultant tumor cell lysate (TCL) can effectively augment such SK-TCL pulsed DC vaccine activity in vivo in anti-tumor activities. In this study, we investigated the specifics and the multi-functional effects of various damaged associated molecular pattern (DAMP) components of the ICD complex for their participation, roles and potential cross talks in activating DCs, as measured by five different functional assays. Results: Among three DAMPs tested, HSP70 and CRT mediate a key role in SK-TCL-induced DC immunity for both CD4+ and CD8+ T cell proliferations in vitro. HSP70 is the most important component, followed by CRT, then HMGB1 in facilitating DC immunity on suppressing metastasis of mouse 4T1 mammary tumors and prolonging survival in test mice. Only HSP70, but not CRT or HMGB1, is effective for the suppression of both granulocytic and monocytic MDSC populations in vivo. Both HSP70 and HMGB1, but not CRT, are essential in activating the expression of three key ICD molecules-associated receptors on test DCs. Each of the three test ICD proteins can exhibit a distinguishable pattern in stimulating the expression of four key chemokines in test DCs. Conclusion: Our findings on the differential roles or effect of various ICD components in activating vaccinated DCs may help formulate new strategies for future cancer vaccine designs.

Original languageEnglish
Article number174
JournalMolecular Cancer
Volume14
Issue number1
DOIs
Publication statusPublished - Sep 24 2015

Fingerprint

Cancer Vaccines
Cell Death
Dendritic Cells
HMGB1 Protein
Neoplasms
Immunity
T-Lymphocytes
shikonin
Precision Medicine
Phytochemicals
Cellular Structures
Chemokines
Immunotherapy
Vaccines
Cell Proliferation
Breast Neoplasms
Neoplasm Metastasis
Survival

Keywords

  • Anti-metastasis
  • Dendritic cell vaccine
  • Immunogenic cells death
  • Shikonin

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Cancer Research

Cite this

Shikonin-enhanced cell immunogenicity of tumor vaccine is mediated by the differential effects of DAMP components. / Lin, Tien-Jen; Lin, Hsin Ting; Chang, Wei Ting; Pradeep Mitapalli, S.; Hsiao, Pei Wen; Yin, Shu Yi; Yang, Ning Sun.

In: Molecular Cancer, Vol. 14, No. 1, 174, 24.09.2015.

Research output: Contribution to journalArticle

Lin, Tien-Jen ; Lin, Hsin Ting ; Chang, Wei Ting ; Pradeep Mitapalli, S. ; Hsiao, Pei Wen ; Yin, Shu Yi ; Yang, Ning Sun. / Shikonin-enhanced cell immunogenicity of tumor vaccine is mediated by the differential effects of DAMP components. In: Molecular Cancer. 2015 ; Vol. 14, No. 1.
@article{6ff203614cf64e94bbc0595441bb42d7,
title = "Shikonin-enhanced cell immunogenicity of tumor vaccine is mediated by the differential effects of DAMP components",
abstract = "Background: The tumor cell lysate-pulsed, dendritic cell (DC)-based cancer vaccine approaches are being actively evaluated for application to cancer immunotherapy, hopefully at a personalized medicine base. There is apparently an emerging technical problem however, the lack of highly efficacious potency in activation of patient's DCs for T-cell priming and the associated process for presenting tumor immunogenicity. Methods: One strategy to address this is to consider the manipulation of the tumor immunogenic cells death (ICD) complex ex-vivo for maximal activation of DC efficacy. In our previous study we showed that phytochemical shikonin (SK) can drastically enhance ICD activity in mouse tumor cells treated ex-vivo, and the resultant tumor cell lysate (TCL) can effectively augment such SK-TCL pulsed DC vaccine activity in vivo in anti-tumor activities. In this study, we investigated the specifics and the multi-functional effects of various damaged associated molecular pattern (DAMP) components of the ICD complex for their participation, roles and potential cross talks in activating DCs, as measured by five different functional assays. Results: Among three DAMPs tested, HSP70 and CRT mediate a key role in SK-TCL-induced DC immunity for both CD4+ and CD8+ T cell proliferations in vitro. HSP70 is the most important component, followed by CRT, then HMGB1 in facilitating DC immunity on suppressing metastasis of mouse 4T1 mammary tumors and prolonging survival in test mice. Only HSP70, but not CRT or HMGB1, is effective for the suppression of both granulocytic and monocytic MDSC populations in vivo. Both HSP70 and HMGB1, but not CRT, are essential in activating the expression of three key ICD molecules-associated receptors on test DCs. Each of the three test ICD proteins can exhibit a distinguishable pattern in stimulating the expression of four key chemokines in test DCs. Conclusion: Our findings on the differential roles or effect of various ICD components in activating vaccinated DCs may help formulate new strategies for future cancer vaccine designs.",
keywords = "Anti-metastasis, Dendritic cell vaccine, Immunogenic cells death, Shikonin",
author = "Tien-Jen Lin and Lin, {Hsin Ting} and Chang, {Wei Ting} and {Pradeep Mitapalli}, S. and Hsiao, {Pei Wen} and Yin, {Shu Yi} and Yang, {Ning Sun}",
year = "2015",
month = "9",
day = "24",
doi = "10.1186/s12943-015-0435-9",
language = "English",
volume = "14",
journal = "Molecular Cancer",
issn = "1476-4598",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - Shikonin-enhanced cell immunogenicity of tumor vaccine is mediated by the differential effects of DAMP components

AU - Lin, Tien-Jen

AU - Lin, Hsin Ting

AU - Chang, Wei Ting

AU - Pradeep Mitapalli, S.

AU - Hsiao, Pei Wen

AU - Yin, Shu Yi

AU - Yang, Ning Sun

PY - 2015/9/24

Y1 - 2015/9/24

N2 - Background: The tumor cell lysate-pulsed, dendritic cell (DC)-based cancer vaccine approaches are being actively evaluated for application to cancer immunotherapy, hopefully at a personalized medicine base. There is apparently an emerging technical problem however, the lack of highly efficacious potency in activation of patient's DCs for T-cell priming and the associated process for presenting tumor immunogenicity. Methods: One strategy to address this is to consider the manipulation of the tumor immunogenic cells death (ICD) complex ex-vivo for maximal activation of DC efficacy. In our previous study we showed that phytochemical shikonin (SK) can drastically enhance ICD activity in mouse tumor cells treated ex-vivo, and the resultant tumor cell lysate (TCL) can effectively augment such SK-TCL pulsed DC vaccine activity in vivo in anti-tumor activities. In this study, we investigated the specifics and the multi-functional effects of various damaged associated molecular pattern (DAMP) components of the ICD complex for their participation, roles and potential cross talks in activating DCs, as measured by five different functional assays. Results: Among three DAMPs tested, HSP70 and CRT mediate a key role in SK-TCL-induced DC immunity for both CD4+ and CD8+ T cell proliferations in vitro. HSP70 is the most important component, followed by CRT, then HMGB1 in facilitating DC immunity on suppressing metastasis of mouse 4T1 mammary tumors and prolonging survival in test mice. Only HSP70, but not CRT or HMGB1, is effective for the suppression of both granulocytic and monocytic MDSC populations in vivo. Both HSP70 and HMGB1, but not CRT, are essential in activating the expression of three key ICD molecules-associated receptors on test DCs. Each of the three test ICD proteins can exhibit a distinguishable pattern in stimulating the expression of four key chemokines in test DCs. Conclusion: Our findings on the differential roles or effect of various ICD components in activating vaccinated DCs may help formulate new strategies for future cancer vaccine designs.

AB - Background: The tumor cell lysate-pulsed, dendritic cell (DC)-based cancer vaccine approaches are being actively evaluated for application to cancer immunotherapy, hopefully at a personalized medicine base. There is apparently an emerging technical problem however, the lack of highly efficacious potency in activation of patient's DCs for T-cell priming and the associated process for presenting tumor immunogenicity. Methods: One strategy to address this is to consider the manipulation of the tumor immunogenic cells death (ICD) complex ex-vivo for maximal activation of DC efficacy. In our previous study we showed that phytochemical shikonin (SK) can drastically enhance ICD activity in mouse tumor cells treated ex-vivo, and the resultant tumor cell lysate (TCL) can effectively augment such SK-TCL pulsed DC vaccine activity in vivo in anti-tumor activities. In this study, we investigated the specifics and the multi-functional effects of various damaged associated molecular pattern (DAMP) components of the ICD complex for their participation, roles and potential cross talks in activating DCs, as measured by five different functional assays. Results: Among three DAMPs tested, HSP70 and CRT mediate a key role in SK-TCL-induced DC immunity for both CD4+ and CD8+ T cell proliferations in vitro. HSP70 is the most important component, followed by CRT, then HMGB1 in facilitating DC immunity on suppressing metastasis of mouse 4T1 mammary tumors and prolonging survival in test mice. Only HSP70, but not CRT or HMGB1, is effective for the suppression of both granulocytic and monocytic MDSC populations in vivo. Both HSP70 and HMGB1, but not CRT, are essential in activating the expression of three key ICD molecules-associated receptors on test DCs. Each of the three test ICD proteins can exhibit a distinguishable pattern in stimulating the expression of four key chemokines in test DCs. Conclusion: Our findings on the differential roles or effect of various ICD components in activating vaccinated DCs may help formulate new strategies for future cancer vaccine designs.

KW - Anti-metastasis

KW - Dendritic cell vaccine

KW - Immunogenic cells death

KW - Shikonin

UR - http://www.scopus.com/inward/record.url?scp=84942324973&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84942324973&partnerID=8YFLogxK

U2 - 10.1186/s12943-015-0435-9

DO - 10.1186/s12943-015-0435-9

M3 - Article

C2 - 26403780

AN - SCOPUS:84942324973

VL - 14

JO - Molecular Cancer

JF - Molecular Cancer

SN - 1476-4598

IS - 1

M1 - 174

ER -