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Rationale and evidence to combine radiation therapy and immunotherapy for cancer treatment

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Abstract

Cancer immunotherapy exploits the immune system’s ability to differentiate between tumor target cells and host cells. Except for limited success against a few tumor types, most immunotherapies have not achieved the desired clinical efficacy until recently. The field of cancer immunotherapy has flourished with a variety of new agents for clinical use, and remarkable progress has been made in the design of effective immunotherapeutic regimens. Furthermore, the therapeutic outcome of these novel agents is enhanced when combined with conventional cancer treatment modalities including radiotherapy (RT). An increasing number of studies have demonstrated the abscopal effect, an immunologic response occurring in cancer sites distant from irradiated areas. The present work reviews studies on the combination between RT and immunotherapy to induce synergistic and abscopal effects involved in cancer immunomodulation. Further insight into the complex interactions between the immune system and cancer cells in the tumor microenvironment, and their modulation by RT, may reveal the abscopal effect as a clinically relevant and reproducible event leading to improved cancer outcome.

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Abbreviations

2D:

Two dimensional

3D:

Three dimensional

CD:

Cluster of differentiation

CTL:

Cytotoxic T lymphocyte

CTLA-4:

Cytotoxic T-lymphocyte-associated protein 4

DC:

Dendritic cell

EBRT:

External beam radiation therapy

Gy:

Gray

HR:

Hazard ratio

ICAM:

Intracellular adhesion molecule

IFN:

Interferon

IGRT:

Image-guided radiation therapy

IL-2:

Interleukin-2

IMRT:

Intensity-modulated radiation therapy

mRCC:

Metastatic renal cell carcinoma

OS:

Overall survival

PD-1:

Programmed death 1

PD-L1:

Programmed death-ligand 1

PSA:

Prostate-specific antigen

RCC:

Renal cell carcinoma

RT:

Radiation therapy

SAbR:

Stereotactic ablative radiation

TAA:

Tumor-associated antigen

TCR:

T cell receptor

TGF:

Transforming growth factor

TIL:

Tumor-infiltrating lymphocyte

Treg:

Regulatory T cell

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Acknowledgments

We thank Dr. Jeffrey Meyer for his contribution to the scientific content of this review and editorial assistance. We thank Dr. Damiana Chiavolini for scientific editing. This review article was not funded.

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Authors and Affiliations

  1. Department of Radiation Oncology, UT Southwestern Medical Center, Dallas, TX, 75390, USA

    Dan Ishihara, Tsuguhide Takeshima, Puneeth Iyengar & Raquibul Hannan

  2. Departments of Immunology and Microbiology, UT Southwestern Medical Center, Dallas, TX, 75204, USA

    Laurentiu Pop

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  3. Tsuguhide Takeshima
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  4. Puneeth Iyengar
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  5. Raquibul Hannan
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Correspondence to Raquibul Hannan.

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Ishihara, D., Pop, L., Takeshima, T. et al. Rationale and evidence to combine radiation therapy and immunotherapy for cancer treatment. Cancer Immunol Immunother 66, 281–298 (2017). https://doi.org/10.1007/s00262-016-1914-6

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  • DOI: https://doi.org/10.1007/s00262-016-1914-6

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