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Table 1 Summary of immuno-oncology agents that could be combined with radiotherapy to improve patient outcomes

From: Reprogramming the tumour microenvironment by radiotherapy: implications for radiotherapy and immunotherapy combinations

Agent

Rationale for combining with radiotherapy

References

CTLA-4

Inhibitor

Immune checkpoint inhibitor. Combination with RT has induced responses in patients where anti-CTLA4 alone had failed. Systemic responses have been observed in patients receiving RT + anti-CTLA4

[3, 7, 8, 16]

PD-1/PD-L1

Inhibitor

Immune checkpoint inhibitor. Systemic responses have been observed when combined with RT. Increased progression free survival and overall survival observed in patients with NSCLC who received RT + anti-PD1

[9, 117, 118]

CD40

Agonist

Enhances DC function, stimulates T-cell trafficking, and activates M1 polarized macrophages, so may overcome immunosuppression. Successful anti-tumour immune responses observed in mice receiving RT + CD40

[29, 50, 52, 81]

TLR

Agonist

Activates T-cells, blocks immunosuppressive effects of MDSCs and tumour associated macrophages. May convert MDSC into immunostimulatory antigen presenting cells

[83,84,85,86,87,88,89,90]

CCL2/5

Inhibitor

Prevents monocyte recruitment to the tumour microenvironment and improves responses to RT in pre-clinical studies

[74,75,76]

Mer-TK

Inhibitor

Inhibits tumour associated macrophages. Tumour regression observed when combined with RT. Induced responses in ‘cold’ tumours with the addition of RT and a TGFβ inhibitor. Delayed metastasis and improved survival when combined with anti-PD1 and RT in pre-clinical studies

[56, 82]

PARP

Inhibitor

Inhibits tumour damage response pathways. Increases T-cell infiltration and increases PD-L1 expression, so could be combined with anti-PD1 and RT

[35,36,37,38]

TGFβ

Inhibitor

Inhibits immunosuppressive effects of TGFβ. Enhances T-cell infiltration in combination with anti-PD1. Combination with RT and anti-PD1 induced greater responses compared to anti-PD1 alone

[72, 73, 93, 95]

PDE5

Inhibitor

Increases T cell infiltration and activation by reducing MDSC function. Improved outcomes observed in patients with metastatic melanoma

[97, 98]