The synergistic effect of radiotherapy and immunotherapy: A promising but not simple partnership

Chajon, É.; Castelli, J.; Marsiglia, H.; Crevoisier, R. de

doi:10.1016/j.critrevonc.2017.01.017

Cited by 109 publications

(83 citation statements)

References 108 publications

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“…This is the reason why several of the immunotherapeutic approaches already applied in clinics or in various phases of clinical trials include DC-based approaches. Recently it has been reported that radiotherapy can positively influence the antitumor immune response and thus could act in synergy with certain immunotherapeutic modalities [41,42,43]. There are data indicating that the potential of irradiation to augment antitumor immunity depends on DC activation [44].…”

Section: Discussionmentioning

confidence: 99%

In Vivo Irradiation of Mice Induces Activation of Dendritic Cells

Persa¹,

Szatmári²,

Sáfrány³

et al. 2018

IJMS

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It is becoming clear that ionizing radiation positively influences certain immune parameters, which opens the possibility for combining radio- and immunotherapies in cancer treatment. The presence of functionally competent dendritic cells (DCs) is crucial in mounting a successful antitumor immune response. While it has been shown that DCs are relatively radioresistant, few and contradictory data are available on how ionizing radiation alters the functional integrity of these cells. Therefore, our objective was to investigate the effect of whole-body irradiation on the function of splenic DCs. C57Bl/6 mice were irradiated with 0.1, 0.25, and 2 Gy X-rays and changes in the phenotype of splenic DCs were compared to unirradiated controls. An increase was seen in DC surface markers influencing DC-T cell interactions. In vivo cytokine production was determined by direct intracellular cytokine staining. Irradiation with 2 Gy induced a 1.6-fold increase in IL-1α production, while the combination of irradiation and lipopolysaccharide (LPS) treatment induced a 3.9-fold increase, indicating a strong synergism between irradiation and LPS stimulation. Interaction of DCs with effector and regulatory T cells was investigated in a mixed lymphocyte reaction. While DCs from control animals induced stronger proliferation of regulatory T cells, DCs from animals irradiated with 2 Gy induced stronger proliferation of effector T cells. Antigen uptake and presentation was investigated by measuring the capacity of DCs to internalize and present ovalbumine (OVA)-derived peptides on their major histocompatibility complex (MHCI) molecules. Irradiation with 2 Gy did not influence antigen uptake or presentation, while low doses stimulated antigen uptake and reduced the level of antigen presentation. In conclusion, high-dose in vivo irradiation induced increased expression of T cell costimulatory markers, enhanced production of proinflammatory cytokines and a stronger stimulation of effector T cell proliferation than that of regulatory T cells. However, it did not influence DC antigen uptake or presentation. On the other hand, low-dose irradiation increased antigen uptake and lowered antigen presentation of DCs, indicating that low- and high-dose irradiation act on different pathways in DCs.

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Section: Discussionmentioning

confidence: 99%

In Vivo Irradiation of Mice Induces Activation of Dendritic Cells

Persa¹,

Szatmári²,

Sáfrány³

et al. 2018

IJMS

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show abstract

“…Radiation expands the intracellular peptide pool and enhances the surface expression of major histocompatibility complex (MHC) class I molecules to increase antigen presentation . Radiation can stimulate the secretion of granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), which can promote the MDSC migration and induce the MDSCs to differentiate into antigen‐presenting cells, then more antigen presentation occurs . Radiation‐damaged dying and stressed cells increase the release of damage‐associated molecular patterns, including ATP, C‐type lectin receptors, and mobility group box 1 protein, to induce dendritic cells maturation .…”

Section: The Basis Of Combining Radiotherapy With Immunotherapymentioning

confidence: 99%

“…According to the results of a gene expression array analysis, local RT increases the production of chemokines responsible for the enhanced recruitment of CD45+ hematopoietic cells into the tumor, including infiltrating dendritic cells with an enhanced functional capacity of tumor antigen cross‐presentation . RT increases the release and recruitment of proinflammatory cytokines, such as reactive oxygen species, interleukin 1β, tumor necrosis factor, transforming growth factor β, interferon (IFN)‐γ, and fibroblast growth factor, that enhance antigen‐specific responses . RT can also increase the induction of many kinds of chemokines, such as CXC‐motif chemokines (CXCL9, 10, 11, and 16), resulting in chemotaxis of T cells into the tumor microenvironment .…”

Section: The Basis Of Combining Radiotherapy With Immunotherapymentioning

confidence: 99%

The Role of Radiation Oncology in Immuno-Oncology

et al. 2019

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“…The “abscopal effect” has been described as a phenomenon of tumor regression distant from the irradiated volume and is theorized to be mediated by the stimulated immune system (40). Further study has identified many immunogenic effects of radiation therapy: increased release of tumor antigen, upregulation of MHC 1 for presentation, activation and migration of dendritic cells, and upregulation of checkpoint expression (40,41). Combination of radiation with chemotherapy has been beneficial in many tumor types underlining the need to study similar potential benefits in combination with immunotherapeutics.…”

Section: Rationale For Combination Immunotherapiesmentioning

confidence: 99%

Rational combinations of immunotherapy for pancreatic ductal adenocarcinoma

Blair¹,

Li²

2017

Chin. Clin. Oncol.

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The complex interaction between the immune system, the tumor and the microenvironment in pancreatic ductal adenocarcinoma (PDA) leads to the resistance of PDA to immunotherapy. To overcome this resistance, combination immunotherapy is being proposed. However, rational combinations that target multiple aspects of the complex anti-tumor immune response are warranted. Novel clinical trials will investigate and optimize the combination immunotherapy for PDA.

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The synergistic effect of radiotherapy and immunotherapy: A promising but not simple partnership

Cited by 109 publications

References 108 publications

In Vivo Irradiation of Mice Induces Activation of Dendritic Cells

In Vivo Irradiation of Mice Induces Activation of Dendritic Cells

The Role of Radiation Oncology in Immuno-Oncology

Rational combinations of immunotherapy for pancreatic ductal adenocarcinoma

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