Immunotherapy with Listeria reduces metastatic breast cancer in young and old mice through different mechanisms

Arthee Jahangir, Dinesh Chandra, Wilber Quispe-Tintaya, Manisha Singh, Benson Chellakkan Selvanesan, Claudia Gravekamp

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Cancer immunotherapy is one of the most promising and benign therapies against metastatic cancer. However, most cancer patients are old and elderly react less efficient to cancer vaccines than young adults, due to T cell unresponsiveness. Here we present data of cancer vaccination in young and old mice with metastatic breast cancer (4T1 model). We tested adaptive and innate immune responses to foreign antigens (Listeria-derived) and self-antigens (tumor-associated antigens (TAA)) and their contribution to elimination of metastases at young and old age. Three different protocols were tested with Listeria: a semi- and exclusive-therapeutic protocol both one-week apart, and an exclusive therapeutic protocol frequently administered. Adaptive and innate immune responses were measured by ELISPOT in correlation with efficacy in the 4T1 model. We found that Listeria induced immunogenic tumor cell death, resulting in CD8 T cell responses to multiple TAA expressed by the 4T1 tumors. Only exclusive therapeutic frequent immunizations were able to overcome immune suppression and to activate TAA- and Listeria-specific CD8 T cells, in correlation with a strong reduction in metastases at both ages. However, MHC class Ia antibodies showed inhibition of CD8 T cell responses to TAA at young but not at old age, and CD8 T cell depletions in vivo demonstrated that the T cells contributed to reduction in metastases at young age only. These results indicate that CD8 T cells activated by Listeria has an antitumor effect at young but not at old age, and that metastases at old age have been eliminated through different mechanism(s).

Original languageEnglish (US)
JournalOncoImmunology
DOIs
StateAccepted/In press - Aug 10 2017

Fingerprint

Listeria
Immunotherapy
Breast Neoplasms
T-Lymphocytes
Neoplasm Antigens
Neoplasm Metastasis
Neoplasms
Adaptive Immunity
Innate Immunity
Enzyme-Linked Immunospot Assay
Cancer Vaccines
Immunoglobulin Isotypes
Autoantigens
Therapeutics
Young Adult
Immunization
Vaccination
Cell Death
Antigens

Keywords

  • Breast cancer
  • immune senescence
  • immune suppression
  • listeria monocytogenes
  • metastases

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology

Cite this

Immunotherapy with Listeria reduces metastatic breast cancer in young and old mice through different mechanisms. / Jahangir, Arthee; Chandra, Dinesh; Quispe-Tintaya, Wilber; Singh, Manisha; Selvanesan, Benson Chellakkan; Gravekamp, Claudia.

In: OncoImmunology, 10.08.2017.

Research output: Contribution to journalArticle

Jahangir, Arthee ; Chandra, Dinesh ; Quispe-Tintaya, Wilber ; Singh, Manisha ; Selvanesan, Benson Chellakkan ; Gravekamp, Claudia. / Immunotherapy with Listeria reduces metastatic breast cancer in young and old mice through different mechanisms. In: OncoImmunology. 2017.
@article{494565e7c2724a8f8e99f2fb656096a8,
title = "Immunotherapy with Listeria reduces metastatic breast cancer in young and old mice through different mechanisms",
abstract = "Cancer immunotherapy is one of the most promising and benign therapies against metastatic cancer. However, most cancer patients are old and elderly react less efficient to cancer vaccines than young adults, due to T cell unresponsiveness. Here we present data of cancer vaccination in young and old mice with metastatic breast cancer (4T1 model). We tested adaptive and innate immune responses to foreign antigens (Listeria-derived) and self-antigens (tumor-associated antigens (TAA)) and their contribution to elimination of metastases at young and old age. Three different protocols were tested with Listeria: a semi- and exclusive-therapeutic protocol both one-week apart, and an exclusive therapeutic protocol frequently administered. Adaptive and innate immune responses were measured by ELISPOT in correlation with efficacy in the 4T1 model. We found that Listeria induced immunogenic tumor cell death, resulting in CD8 T cell responses to multiple TAA expressed by the 4T1 tumors. Only exclusive therapeutic frequent immunizations were able to overcome immune suppression and to activate TAA- and Listeria-specific CD8 T cells, in correlation with a strong reduction in metastases at both ages. However, MHC class Ia antibodies showed inhibition of CD8 T cell responses to TAA at young but not at old age, and CD8 T cell depletions in vivo demonstrated that the T cells contributed to reduction in metastases at young age only. These results indicate that CD8 T cells activated by Listeria has an antitumor effect at young but not at old age, and that metastases at old age have been eliminated through different mechanism(s).",
keywords = "Breast cancer, immune senescence, immune suppression, listeria monocytogenes, metastases",
author = "Arthee Jahangir and Dinesh Chandra and Wilber Quispe-Tintaya and Manisha Singh and Selvanesan, {Benson Chellakkan} and Claudia Gravekamp",
year = "2017",
month = "8",
day = "10",
doi = "10.1080/2162402X.2017.1342025",
language = "English (US)",
journal = "OncoImmunology",
issn = "2162-4011",
publisher = "Landes Bioscience",

}

TY - JOUR

T1 - Immunotherapy with Listeria reduces metastatic breast cancer in young and old mice through different mechanisms

AU - Jahangir, Arthee

AU - Chandra, Dinesh

AU - Quispe-Tintaya, Wilber

AU - Singh, Manisha

AU - Selvanesan, Benson Chellakkan

AU - Gravekamp, Claudia

PY - 2017/8/10

Y1 - 2017/8/10

N2 - Cancer immunotherapy is one of the most promising and benign therapies against metastatic cancer. However, most cancer patients are old and elderly react less efficient to cancer vaccines than young adults, due to T cell unresponsiveness. Here we present data of cancer vaccination in young and old mice with metastatic breast cancer (4T1 model). We tested adaptive and innate immune responses to foreign antigens (Listeria-derived) and self-antigens (tumor-associated antigens (TAA)) and their contribution to elimination of metastases at young and old age. Three different protocols were tested with Listeria: a semi- and exclusive-therapeutic protocol both one-week apart, and an exclusive therapeutic protocol frequently administered. Adaptive and innate immune responses were measured by ELISPOT in correlation with efficacy in the 4T1 model. We found that Listeria induced immunogenic tumor cell death, resulting in CD8 T cell responses to multiple TAA expressed by the 4T1 tumors. Only exclusive therapeutic frequent immunizations were able to overcome immune suppression and to activate TAA- and Listeria-specific CD8 T cells, in correlation with a strong reduction in metastases at both ages. However, MHC class Ia antibodies showed inhibition of CD8 T cell responses to TAA at young but not at old age, and CD8 T cell depletions in vivo demonstrated that the T cells contributed to reduction in metastases at young age only. These results indicate that CD8 T cells activated by Listeria has an antitumor effect at young but not at old age, and that metastases at old age have been eliminated through different mechanism(s).

AB - Cancer immunotherapy is one of the most promising and benign therapies against metastatic cancer. However, most cancer patients are old and elderly react less efficient to cancer vaccines than young adults, due to T cell unresponsiveness. Here we present data of cancer vaccination in young and old mice with metastatic breast cancer (4T1 model). We tested adaptive and innate immune responses to foreign antigens (Listeria-derived) and self-antigens (tumor-associated antigens (TAA)) and their contribution to elimination of metastases at young and old age. Three different protocols were tested with Listeria: a semi- and exclusive-therapeutic protocol both one-week apart, and an exclusive therapeutic protocol frequently administered. Adaptive and innate immune responses were measured by ELISPOT in correlation with efficacy in the 4T1 model. We found that Listeria induced immunogenic tumor cell death, resulting in CD8 T cell responses to multiple TAA expressed by the 4T1 tumors. Only exclusive therapeutic frequent immunizations were able to overcome immune suppression and to activate TAA- and Listeria-specific CD8 T cells, in correlation with a strong reduction in metastases at both ages. However, MHC class Ia antibodies showed inhibition of CD8 T cell responses to TAA at young but not at old age, and CD8 T cell depletions in vivo demonstrated that the T cells contributed to reduction in metastases at young age only. These results indicate that CD8 T cells activated by Listeria has an antitumor effect at young but not at old age, and that metastases at old age have been eliminated through different mechanism(s).

KW - Breast cancer

KW - immune senescence

KW - immune suppression

KW - listeria monocytogenes

KW - metastases

UR - http://www.scopus.com/inward/record.url?scp=85027383636&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85027383636&partnerID=8YFLogxK

U2 - 10.1080/2162402X.2017.1342025

DO - 10.1080/2162402X.2017.1342025

M3 - Article

AN - SCOPUS:85027383636

JO - OncoImmunology

JF - OncoImmunology

SN - 2162-4011

ER -