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Cancer Immunology, Immunotherapy

, Volume 65, Issue 7, pp 787–796 | Cite as

Improving cancer immunotherapy with DNA methyltransferase inhibitors

  • Mohammad H. Saleh
  • Lei Wang
  • Michael S. Goldberg
Focussed Research Review

Abstract

Immunotherapy confers durable clinical benefit to melanoma, lung, and kidney cancer patients. Challengingly, most other solid tumors, including ovarian carcinoma, are not particularly responsive to immunotherapy, so combination with a complementary therapy may be beneficial. Recent findings suggest that epigenetic modifying drugs can prime antitumor immunity by increasing expression of tumor-associated antigens, chemokines, and activating ligands by cancer cells as well as cytokines by immune cells. This review, drawing from both preclinical and clinical data, describes some of the mechanisms of action that enable DNA methyltransferase inhibitors to facilitate the establishment of antitumor immunity.

Keywords

CITIM 2015 Epigenetic modifier DNA methyltransferase inhibitor Decitabine Immunotherapy Ovarian cancer 

Abbreviations

AML

Acute myeloid leukemia

AZA

Azacitidine

CLL

Chronic lymphocytic leukemia

CTA

Cancer testis antigen

CTL

Cytotoxic T lymphocyte

DAC

Decitabine

DNMT

DNA methyltransferases

DNMTi

DNA methyltransferase inhibitor

HDAC

Histone deacetylase

MAGE

Melanoma-associated antigen

MDS

Myelodysplastic syndrome

MDSC

Myeloid-derived suppressor cell

MHC I

Major histocompatibility complex class I

NK cells

Natural killer cells

NKG2D

Natural-killer group 2, member D

NSCLC

Non-small cell lung cancer

KIR

Killer immunoglobulin-like receptor

Tregs

Regulatory T cells

Notes

Acknowledgments

We thank the Ovarian Cancer Research Fund (Liz Tilberis Scholar award) and the Susan F. Smith Center for Women’s Cancer for supporting this work.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Mohammad H. Saleh
    • 1
  • Lei Wang
    • 1
  • Michael S. Goldberg
    • 1
  1. 1.Department of Cancer Immunology and VirologyDana-Farber Cancer InstituteBostonUSA

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