Oncotarget

Research Papers:

Combination therapy with dendritic cells and lenalidomide is an effective approach to enhance antitumor immunity in a mouse colon cancer model

Manh-Cuong Vo, Thanh-Nhan Nguyen-Pham, Hyun-Ju Lee, Thangaraj Jaya Lakshmi, Seoyun Yang, Sung-Hoon Jung, Hyeoung-Joon Kim and Je-Jung Lee _

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Oncotarget. 2017; 8:27252-27262. https://doi.org/10.18632/oncotarget.15917

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Abstract

Manh-Cuong Vo1,*, Thanh-Nhan Nguyen-Pham1,2,*, Hyun-Ju Lee1,2, Thangaraj Jaya Lakshmi1,2, Seoyun Yang1,2, Sung-Hoon Jung1,2, Hyeoung-Joon Kim2, Je-Jung Lee1,2

1Research Center for Cancer Immunotherapy, Chonnam National University Hwasun Hospital, Hwasun, Jeollanamdo, Republic of Korea

2Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Hwasun, Jeollanamdo, Republic of Korea

*These authors have contributed equally to this work

Correspondence to:

Je-Jung Lee, email: drjejung@chonnam.ac.kr

Keywords: lenalidomide, dendritic cells, mouse colon cancer

Received: July 06, 2016     Accepted: February 20, 2017     Published: March 06, 2017

ABSTRACT

In this study, we investigated efficacy of lenalidomide in combination with tumor antigen-loaded dendritic cells (DCs) in murine colon cancer model. MC-38 cell lines were injected subcutaneously to establish colon cancer-bearing mice. After tumor growth, lenalidomide (50 mg/kg/day) was injected intraperitoneally on 3 consecutive days in combination with tumor antigen-loaded DC vaccination on days 8, 12, 16, and 20. The tumor antigen-loaded DCs plus lenalidomide combination treatment exhibited a significant inhibition of tumor growth compared with the other groups. These effects were associated with a reduction in immune suppressor cells, such as myeloid-derived suppressor cells and regulatory T cells, with the induction of immune effector cells, such as natural killer cells, CD4+ T cells and CD8+ T cells in spleen, and with the activation of cytotoxic T lymphocytes and NK cells. This study suggests that a combination of tumor antigen-loaded DC vaccination and lenalidomide synergistically enhanced antitumor immune response in the murine colon cancer model, by inhibiting the generation of immune suppressive cells and recovery of effector cells, and demonstrated superior polarization of Th1/Th2 balance in favor of Th1 immune response. This combination approach with DCs and lenalidomide may provide a new therapeutic option to improve the treatment of colon cancer.


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