Immune reactivation by cell-free fetal DNA in healthy pregnancies re-purposed to target tumors: Novel checkpoint inhibition in cancer therapeutics

Elizabeth Ann L Enninga, Wendy K. Nevala, Shernan G. Holtan, Svetomir Nenad Markovic

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

The role of the immune system in cancer progression has become increasingly evident over the past decade. Chronic inflammation in the promotion of tumorigenesis is well established, and cancer-associated tolerance/immune evasion has long been appreciated. Recent developments of immunotherapies targeting cancer-associated inflammation and immune tolerance, such as cancer vaccines, cell therapies, neutralizing antibodies, and immune checkpoint inhibitors, have shown promising clinical results. However, despite significant therapeutic advances, most patients diagnosed with metastatic cancer still succumb to their malignancy. Treatments are often toxic, and the financial burden of novel therapies is significant. Thus, new methods for utilizing similar biological systems to compare complex biological processes can give us new hypotheses for combating cancer. One such approach is comparing trophoblastic growth and regulation to tumor invasion and immune escape. Novel concepts regarding immune activation in pregnancy, especially reactivation of the immune system at labor through toll like receptor engagement by fetal derived DNA, may be applicable to cancer immunotherapy. This review summarizes mechanisms of inflammation in cancer, current immunotherapies used in the clinic, and suggestions for looking beyond oncology for novel methods to reverse cancer-associated tolerance and immunologic exhaustion utilizing mechanisms encountered in normal human pregnancy.

Original languageEnglish (US)
Article number00424
JournalFrontiers in Immunology
Volume6
Issue numberAUG
DOIs
StatePublished - 2015

Fingerprint

Pregnancy
DNA
Neoplasms
Immunotherapy
Therapeutics
Inflammation
Immune System
Tumor Escape
Biological Phenomena
Immune Evasion
Active Immunotherapy
Immune Tolerance
Cancer Vaccines
Poisons
Toll-Like Receptors
Cell- and Tissue-Based Therapy
Neutralizing Antibodies
Carcinogenesis
Growth

Keywords

  • Cell-free fetal DNA
  • Circulating tumor DNA
  • Immunotherapy
  • Inflammation
  • Toll like receptors

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Immune reactivation by cell-free fetal DNA in healthy pregnancies re-purposed to target tumors : Novel checkpoint inhibition in cancer therapeutics. / Enninga, Elizabeth Ann L; Nevala, Wendy K.; Holtan, Shernan G.; Markovic, Svetomir Nenad.

In: Frontiers in Immunology, Vol. 6, No. AUG, 00424, 2015.

Research output: Contribution to journalArticle

@article{ab57fd2c0f924f59bd70cd5dd30b434c,
title = "Immune reactivation by cell-free fetal DNA in healthy pregnancies re-purposed to target tumors: Novel checkpoint inhibition in cancer therapeutics",
abstract = "The role of the immune system in cancer progression has become increasingly evident over the past decade. Chronic inflammation in the promotion of tumorigenesis is well established, and cancer-associated tolerance/immune evasion has long been appreciated. Recent developments of immunotherapies targeting cancer-associated inflammation and immune tolerance, such as cancer vaccines, cell therapies, neutralizing antibodies, and immune checkpoint inhibitors, have shown promising clinical results. However, despite significant therapeutic advances, most patients diagnosed with metastatic cancer still succumb to their malignancy. Treatments are often toxic, and the financial burden of novel therapies is significant. Thus, new methods for utilizing similar biological systems to compare complex biological processes can give us new hypotheses for combating cancer. One such approach is comparing trophoblastic growth and regulation to tumor invasion and immune escape. Novel concepts regarding immune activation in pregnancy, especially reactivation of the immune system at labor through toll like receptor engagement by fetal derived DNA, may be applicable to cancer immunotherapy. This review summarizes mechanisms of inflammation in cancer, current immunotherapies used in the clinic, and suggestions for looking beyond oncology for novel methods to reverse cancer-associated tolerance and immunologic exhaustion utilizing mechanisms encountered in normal human pregnancy.",
keywords = "Cell-free fetal DNA, Circulating tumor DNA, Immunotherapy, Inflammation, Toll like receptors",
author = "Enninga, {Elizabeth Ann L} and Nevala, {Wendy K.} and Holtan, {Shernan G.} and Markovic, {Svetomir Nenad}",
year = "2015",
doi = "10.3389/fimmu.2015.00424",
language = "English (US)",
volume = "6",
journal = "Frontiers in Immunology",
issn = "1664-3224",
publisher = "Frontiers Media S. A.",
number = "AUG",

}

TY - JOUR

T1 - Immune reactivation by cell-free fetal DNA in healthy pregnancies re-purposed to target tumors

T2 - Novel checkpoint inhibition in cancer therapeutics

AU - Enninga, Elizabeth Ann L

AU - Nevala, Wendy K.

AU - Holtan, Shernan G.

AU - Markovic, Svetomir Nenad

PY - 2015

Y1 - 2015

N2 - The role of the immune system in cancer progression has become increasingly evident over the past decade. Chronic inflammation in the promotion of tumorigenesis is well established, and cancer-associated tolerance/immune evasion has long been appreciated. Recent developments of immunotherapies targeting cancer-associated inflammation and immune tolerance, such as cancer vaccines, cell therapies, neutralizing antibodies, and immune checkpoint inhibitors, have shown promising clinical results. However, despite significant therapeutic advances, most patients diagnosed with metastatic cancer still succumb to their malignancy. Treatments are often toxic, and the financial burden of novel therapies is significant. Thus, new methods for utilizing similar biological systems to compare complex biological processes can give us new hypotheses for combating cancer. One such approach is comparing trophoblastic growth and regulation to tumor invasion and immune escape. Novel concepts regarding immune activation in pregnancy, especially reactivation of the immune system at labor through toll like receptor engagement by fetal derived DNA, may be applicable to cancer immunotherapy. This review summarizes mechanisms of inflammation in cancer, current immunotherapies used in the clinic, and suggestions for looking beyond oncology for novel methods to reverse cancer-associated tolerance and immunologic exhaustion utilizing mechanisms encountered in normal human pregnancy.

AB - The role of the immune system in cancer progression has become increasingly evident over the past decade. Chronic inflammation in the promotion of tumorigenesis is well established, and cancer-associated tolerance/immune evasion has long been appreciated. Recent developments of immunotherapies targeting cancer-associated inflammation and immune tolerance, such as cancer vaccines, cell therapies, neutralizing antibodies, and immune checkpoint inhibitors, have shown promising clinical results. However, despite significant therapeutic advances, most patients diagnosed with metastatic cancer still succumb to their malignancy. Treatments are often toxic, and the financial burden of novel therapies is significant. Thus, new methods for utilizing similar biological systems to compare complex biological processes can give us new hypotheses for combating cancer. One such approach is comparing trophoblastic growth and regulation to tumor invasion and immune escape. Novel concepts regarding immune activation in pregnancy, especially reactivation of the immune system at labor through toll like receptor engagement by fetal derived DNA, may be applicable to cancer immunotherapy. This review summarizes mechanisms of inflammation in cancer, current immunotherapies used in the clinic, and suggestions for looking beyond oncology for novel methods to reverse cancer-associated tolerance and immunologic exhaustion utilizing mechanisms encountered in normal human pregnancy.

KW - Cell-free fetal DNA

KW - Circulating tumor DNA

KW - Immunotherapy

KW - Inflammation

KW - Toll like receptors

UR - http://www.scopus.com/inward/record.url?scp=84941272751&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84941272751&partnerID=8YFLogxK

U2 - 10.3389/fimmu.2015.00424

DO - 10.3389/fimmu.2015.00424

M3 - Article

AN - SCOPUS:84941272751

VL - 6

JO - Frontiers in Immunology

JF - Frontiers in Immunology

SN - 1664-3224

IS - AUG

M1 - 00424

ER -