Immunoediting and antigen loss: Overcoming the Achilles heel of immunotherapy with antigen non-specific therapies

Arta M Monjazeb, Anthony E. Zamora, Steven K. Grossenbacher, Annie Mirsoian, Gail D. Sckisel, William J Murphy

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Cancer immunotherapy has emerged as a mainstream therapy option in the battle against cancer. Pre-clinical data demonstrates the ability of immunotherapy to harness the immune system to fight disseminated malignancy. Clinical translation has failed to recapitulate the promising results of pre-clinical studies although there have been some successes. In this review we explore some of the short-comings of cancer immunotherapy that have limited successful clinical translation. We will give special consideration to what we consider the most formidable hurdle to successful cancer immunotherapy: tumor-induced immune suppression and immune escape. We will discuss the need for antigen-specific immune responses for successful immunotherapy but also consider the need for antigen specificity as an Achilles heel of immunotherapy given tumor heterogeneity, immune editing, and antigen loss. Finally, we will discuss how combinatorial strategies may overcome some of the pitfalls of antigen specificity and highlight recent studies from our lab which suggest that the induction of antigen non-specific immune responses may also produce robust anti-tumor effects and bypass the need for antigen specificity.

Original languageEnglish (US)
Article number00197
JournalFrontiers in Oncology
Volume3 JUL
DOIs
StatePublished - 2013

Fingerprint

Immunotherapy
Antigens
Neoplasms
Therapeutics
Histocompatibility Antigens Class II
Immune System

Keywords

  • Bystander T-cells
  • Cancer immunotherapy
  • Immune suppression
  • Immune surveillance
  • Immune tolerance
  • Radiotherapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Immunoediting and antigen loss : Overcoming the Achilles heel of immunotherapy with antigen non-specific therapies. / Monjazeb, Arta M; Zamora, Anthony E.; Grossenbacher, Steven K.; Mirsoian, Annie; Sckisel, Gail D.; Murphy, William J.

In: Frontiers in Oncology, Vol. 3 JUL, 00197, 2013.

Research output: Contribution to journalArticle

Monjazeb, Arta M ; Zamora, Anthony E. ; Grossenbacher, Steven K. ; Mirsoian, Annie ; Sckisel, Gail D. ; Murphy, William J. / Immunoediting and antigen loss : Overcoming the Achilles heel of immunotherapy with antigen non-specific therapies. In: Frontiers in Oncology. 2013 ; Vol. 3 JUL.
@article{8276021ddf624c30bfd9002d051707e3,
title = "Immunoediting and antigen loss: Overcoming the Achilles heel of immunotherapy with antigen non-specific therapies",
abstract = "Cancer immunotherapy has emerged as a mainstream therapy option in the battle against cancer. Pre-clinical data demonstrates the ability of immunotherapy to harness the immune system to fight disseminated malignancy. Clinical translation has failed to recapitulate the promising results of pre-clinical studies although there have been some successes. In this review we explore some of the short-comings of cancer immunotherapy that have limited successful clinical translation. We will give special consideration to what we consider the most formidable hurdle to successful cancer immunotherapy: tumor-induced immune suppression and immune escape. We will discuss the need for antigen-specific immune responses for successful immunotherapy but also consider the need for antigen specificity as an Achilles heel of immunotherapy given tumor heterogeneity, immune editing, and antigen loss. Finally, we will discuss how combinatorial strategies may overcome some of the pitfalls of antigen specificity and highlight recent studies from our lab which suggest that the induction of antigen non-specific immune responses may also produce robust anti-tumor effects and bypass the need for antigen specificity.",
keywords = "Bystander T-cells, Cancer immunotherapy, Immune suppression, Immune surveillance, Immune tolerance, Radiotherapy",
author = "Monjazeb, {Arta M} and Zamora, {Anthony E.} and Grossenbacher, {Steven K.} and Annie Mirsoian and Sckisel, {Gail D.} and Murphy, {William J}",
year = "2013",
doi = "10.3389/fonc.2013.00197",
language = "English (US)",
volume = "3 JUL",
journal = "Frontiers in Oncology",
issn = "2234-943X",
publisher = "Frontiers Media S. A.",

}

TY - JOUR

T1 - Immunoediting and antigen loss

T2 - Overcoming the Achilles heel of immunotherapy with antigen non-specific therapies

AU - Monjazeb, Arta M

AU - Zamora, Anthony E.

AU - Grossenbacher, Steven K.

AU - Mirsoian, Annie

AU - Sckisel, Gail D.

AU - Murphy, William J

PY - 2013

Y1 - 2013

N2 - Cancer immunotherapy has emerged as a mainstream therapy option in the battle against cancer. Pre-clinical data demonstrates the ability of immunotherapy to harness the immune system to fight disseminated malignancy. Clinical translation has failed to recapitulate the promising results of pre-clinical studies although there have been some successes. In this review we explore some of the short-comings of cancer immunotherapy that have limited successful clinical translation. We will give special consideration to what we consider the most formidable hurdle to successful cancer immunotherapy: tumor-induced immune suppression and immune escape. We will discuss the need for antigen-specific immune responses for successful immunotherapy but also consider the need for antigen specificity as an Achilles heel of immunotherapy given tumor heterogeneity, immune editing, and antigen loss. Finally, we will discuss how combinatorial strategies may overcome some of the pitfalls of antigen specificity and highlight recent studies from our lab which suggest that the induction of antigen non-specific immune responses may also produce robust anti-tumor effects and bypass the need for antigen specificity.

AB - Cancer immunotherapy has emerged as a mainstream therapy option in the battle against cancer. Pre-clinical data demonstrates the ability of immunotherapy to harness the immune system to fight disseminated malignancy. Clinical translation has failed to recapitulate the promising results of pre-clinical studies although there have been some successes. In this review we explore some of the short-comings of cancer immunotherapy that have limited successful clinical translation. We will give special consideration to what we consider the most formidable hurdle to successful cancer immunotherapy: tumor-induced immune suppression and immune escape. We will discuss the need for antigen-specific immune responses for successful immunotherapy but also consider the need for antigen specificity as an Achilles heel of immunotherapy given tumor heterogeneity, immune editing, and antigen loss. Finally, we will discuss how combinatorial strategies may overcome some of the pitfalls of antigen specificity and highlight recent studies from our lab which suggest that the induction of antigen non-specific immune responses may also produce robust anti-tumor effects and bypass the need for antigen specificity.

KW - Bystander T-cells

KW - Cancer immunotherapy

KW - Immune suppression

KW - Immune surveillance

KW - Immune tolerance

KW - Radiotherapy

UR - http://www.scopus.com/inward/record.url?scp=84890490882&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84890490882&partnerID=8YFLogxK

U2 - 10.3389/fonc.2013.00197

DO - 10.3389/fonc.2013.00197

M3 - Article

AN - SCOPUS:84890490882

VL - 3 JUL

JO - Frontiers in Oncology

JF - Frontiers in Oncology

SN - 2234-943X

M1 - 00197

ER -