Chemotherapy acts as an adjuvant to convert the tumor microenvironment into a highly permissive state for vaccination-induced antitumor immunity

Tae Heung Kang, Chih Ping Mao, Sung Yong Lee, Alexander Chen, Ji Hyun Lee, Tae Woo Kim, Ronald D. Alvarez, Richard B S Roden, Drew Pardoll, Chien Fu Hung, T. C. Wu

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Multiple classes of pharmacologic agents have the potential to induce the expression and release of proinflammatory factors from dying tumor cells. As a result, these cells can in theory elicit an immune response through various defined mechanisms to permanently eradicate disseminated cancer. However, the impact of chemotherapy on the tumor-specific immune response in the context of the tumor microenvironment is largely unknown. Within the tumor microenvironment, the immune response promoted by chemotherapy is antagonized by an immune-suppressive milieu, and the balance of these opposing forces dictates the clinical course of disease. Here, we report that high antigen exposure within the tumor microenvironment following chemotherapy is sufficient to skew this balance in favor of a productive immune response. In elevating antigen exposure, chemotherapy can achieve long-term control of tumor progression without the need of an additional adjuvant. We found that chemotherapy initiated this phenomenon in the tumor microenvironment through an accumulation of dendritic cells, which stimulated CD8+ T cells and the type I IFN pathway. From this conceptual base, we developed a simple approach to cancer therapy combining chemotherapy and vaccination that may be widely applicable. Cancer Res; 73(8); 2493-504.

Original languageEnglish
Pages (from-to)2493-2504
Number of pages12
JournalCancer Research
Volume73
Issue number8
DOIs
Publication statusPublished - 2013 Apr 15

Fingerprint

Tumor Microenvironment
Immunity
Vaccination
Drug Therapy
Neoplasms
Antigens
Dendritic Cells
T-Lymphocytes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Chemotherapy acts as an adjuvant to convert the tumor microenvironment into a highly permissive state for vaccination-induced antitumor immunity. / Kang, Tae Heung; Mao, Chih Ping; Lee, Sung Yong; Chen, Alexander; Lee, Ji Hyun; Kim, Tae Woo; Alvarez, Ronald D.; Roden, Richard B S; Pardoll, Drew; Hung, Chien Fu; Wu, T. C.

In: Cancer Research, Vol. 73, No. 8, 15.04.2013, p. 2493-2504.

Research output: Contribution to journalArticle

Kang, Tae Heung ; Mao, Chih Ping ; Lee, Sung Yong ; Chen, Alexander ; Lee, Ji Hyun ; Kim, Tae Woo ; Alvarez, Ronald D. ; Roden, Richard B S ; Pardoll, Drew ; Hung, Chien Fu ; Wu, T. C. / Chemotherapy acts as an adjuvant to convert the tumor microenvironment into a highly permissive state for vaccination-induced antitumor immunity. In: Cancer Research. 2013 ; Vol. 73, No. 8. pp. 2493-2504.
@article{de040fcf77ed4ee9905da45e9530efbb,
title = "Chemotherapy acts as an adjuvant to convert the tumor microenvironment into a highly permissive state for vaccination-induced antitumor immunity",
abstract = "Multiple classes of pharmacologic agents have the potential to induce the expression and release of proinflammatory factors from dying tumor cells. As a result, these cells can in theory elicit an immune response through various defined mechanisms to permanently eradicate disseminated cancer. However, the impact of chemotherapy on the tumor-specific immune response in the context of the tumor microenvironment is largely unknown. Within the tumor microenvironment, the immune response promoted by chemotherapy is antagonized by an immune-suppressive milieu, and the balance of these opposing forces dictates the clinical course of disease. Here, we report that high antigen exposure within the tumor microenvironment following chemotherapy is sufficient to skew this balance in favor of a productive immune response. In elevating antigen exposure, chemotherapy can achieve long-term control of tumor progression without the need of an additional adjuvant. We found that chemotherapy initiated this phenomenon in the tumor microenvironment through an accumulation of dendritic cells, which stimulated CD8+ T cells and the type I IFN pathway. From this conceptual base, we developed a simple approach to cancer therapy combining chemotherapy and vaccination that may be widely applicable. Cancer Res; 73(8); 2493-504.",
author = "Kang, {Tae Heung} and Mao, {Chih Ping} and Lee, {Sung Yong} and Alexander Chen and Lee, {Ji Hyun} and Kim, {Tae Woo} and Alvarez, {Ronald D.} and Roden, {Richard B S} and Drew Pardoll and Hung, {Chien Fu} and Wu, {T. C.}",
year = "2013",
month = "4",
day = "15",
doi = "10.1158/0008-5472.CAN-12-4241",
language = "English",
volume = "73",
pages = "2493--2504",
journal = "Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "8",

}

TY - JOUR

T1 - Chemotherapy acts as an adjuvant to convert the tumor microenvironment into a highly permissive state for vaccination-induced antitumor immunity

AU - Kang, Tae Heung

AU - Mao, Chih Ping

AU - Lee, Sung Yong

AU - Chen, Alexander

AU - Lee, Ji Hyun

AU - Kim, Tae Woo

AU - Alvarez, Ronald D.

AU - Roden, Richard B S

AU - Pardoll, Drew

AU - Hung, Chien Fu

AU - Wu, T. C.

PY - 2013/4/15

Y1 - 2013/4/15

N2 - Multiple classes of pharmacologic agents have the potential to induce the expression and release of proinflammatory factors from dying tumor cells. As a result, these cells can in theory elicit an immune response through various defined mechanisms to permanently eradicate disseminated cancer. However, the impact of chemotherapy on the tumor-specific immune response in the context of the tumor microenvironment is largely unknown. Within the tumor microenvironment, the immune response promoted by chemotherapy is antagonized by an immune-suppressive milieu, and the balance of these opposing forces dictates the clinical course of disease. Here, we report that high antigen exposure within the tumor microenvironment following chemotherapy is sufficient to skew this balance in favor of a productive immune response. In elevating antigen exposure, chemotherapy can achieve long-term control of tumor progression without the need of an additional adjuvant. We found that chemotherapy initiated this phenomenon in the tumor microenvironment through an accumulation of dendritic cells, which stimulated CD8+ T cells and the type I IFN pathway. From this conceptual base, we developed a simple approach to cancer therapy combining chemotherapy and vaccination that may be widely applicable. Cancer Res; 73(8); 2493-504.

AB - Multiple classes of pharmacologic agents have the potential to induce the expression and release of proinflammatory factors from dying tumor cells. As a result, these cells can in theory elicit an immune response through various defined mechanisms to permanently eradicate disseminated cancer. However, the impact of chemotherapy on the tumor-specific immune response in the context of the tumor microenvironment is largely unknown. Within the tumor microenvironment, the immune response promoted by chemotherapy is antagonized by an immune-suppressive milieu, and the balance of these opposing forces dictates the clinical course of disease. Here, we report that high antigen exposure within the tumor microenvironment following chemotherapy is sufficient to skew this balance in favor of a productive immune response. In elevating antigen exposure, chemotherapy can achieve long-term control of tumor progression without the need of an additional adjuvant. We found that chemotherapy initiated this phenomenon in the tumor microenvironment through an accumulation of dendritic cells, which stimulated CD8+ T cells and the type I IFN pathway. From this conceptual base, we developed a simple approach to cancer therapy combining chemotherapy and vaccination that may be widely applicable. Cancer Res; 73(8); 2493-504.

UR - http://www.scopus.com/inward/record.url?scp=84876961766&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84876961766&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-12-4241

DO - 10.1158/0008-5472.CAN-12-4241

M3 - Article

VL - 73

SP - 2493

EP - 2504

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 8

ER -