Table 1 Highlighted clinical and preclinical studies utilizing LDRT and immunotherapy

Preclinical

LD-TBI and IL-2

Synergism

Melanoma with lung metastasis

(B16F1 malignant melanoma in mice)

0.75 Gy/f

Significant increase in NK cells and macrophages infiltrating the metastatic site. CD122 + expression and NK and T cells in peripheral blood and spleen were significantly increased.

[35]

Preclinical

LD-TBI and IL-2

Melanoma (B16F1)

murine metastatic malignant melanoma model

0.75 Gy/f

The combination of high doses of IL-2 and LDWBI (either dose) resulted in a significant reduction in tumor load and an increase in tumor invasion of NK cells.

[36]

Preclinical

Localized radiotherapy + LDWBI + gene therapy by intratumor injection of Egr-mIL-18- B7.1

Melanoma (B16)

0.075 Gy

Improved survival rate, reduced tumor weight and lung metastasis, inhibition of tumor capillaries. Enhanced activity of NK cells and cytotoxic T lymphocyte (CTL), and increased secretion of interferon-γ (IFN-γ).

[37]

Clinical stage-IV melanoma

LDRT + PD1

Liver metastasis in Advanced melanoma

1.4 Gy/4f (5.6 Gy)

Complete response was observed in a, receiving LDRT to liver metastases. The patient was pretreated with ICB and T-cell therapy.

[21]

Preclinical

LDRT

+PD-L1

B16 melanoma mouse model

500 cGy

Significantly reduced tumor growth rate, improved survival, and an increase of 40% complete response rate.

[38]

Preclinical

Abscopal

+IC+

αCTLA4 + WBRT

Melanoma mouse model

Whole brain LDRT (WBRT)

4 Gy × 1f

Significantly improved survival and cranial metastatic tumor control

[22]

Preclinical

TRT+

ICB

Immunologically cold syngeneic B78 melanoma tumors

Low dose of targeted radionuclide therapy (TRT)

Improved NK cells, tumor infiltrating myeloid cells along with increase in the ratio of CD8+ to suppressor T regulatory cells

[34]

Preclinical clinical

Oncolytic Virus + LDRT + α-PD1

Melanoma (B16F1) mouse model

6 Gy

Reduced tumor growth and prolonged survival via conversion of ‘cold’ tumors to ‘hot’, via a CD8+ T cell-dependent and IL-1α-dependent mechanism and increased PD-1/PD-L1 expression.

[39]

Clinical

Oncolytic Virus

+LDRT

+ICB

PD-1-refractory patient with cutaneous squamous cell carcinoma

2.5 Gy/1f for 20 fractions

Prolonged control and survival.

[39]

Preclinical

vaccinia virus to express NIS before RT ¹³¹I treatment

Prostate Carcinoma Cells

-

Markedly improved the accumulation of radioiodine mediated by intratumoral NIS protein expression, and the combination suppressed prostate carcinoma cells compared to either OVs alone or ¹³¹I alone

[40]

Preclinical

¹³¹I-iodide + vaccinia virus (GLV-1h153)

orthotopic triple-negative breast cancer (TNBC) murine model

-

Resulted in a 6-fold increase in tumor regression as compared to the virus-only treatment group.

[41]