Table 3 TLR-based antitumor treatment in vivo or in vitro through agonist targeting

TLR1/TLR2

Pam3Cys-SK4

n/a

n/a

n/a

Murine GL261 implanted C57BL/6 J mouse

Survival benefit

[95]

Lipoprotein

Antigen-specific T-cells

n/a

n/a

Murine GL261 implanted C57BL/6 J mouse

Survival benefit

Immune memory development

[130]

TLR2

Pam3Cys-SK4

n/a

GSCs of G261

Increased GSC invasion

n/a

n/a

[88]

Pam3Cys-SK4

n/a

U87, U118

GSC differentiation

n/a

n/a

[86]

Pam3Cys-SK4

TMZ

U87, U118

GSC differentiation

Increased cell death

n/a

n/a

[86]

TLR3

Poly (I:C)

n/a

n/a

n/a

Murine GL261 implanted C57BL/6 J mouse

Rat CNS-1 implanted Lewis rats

Not effective

[69, 95]

Poly (I:C)

n/a

n/a

n/a

Murine GL261 implanted C57BL/6 J mouse

DC-dependent survival benefit

[187]

Poly (I:C)

Anti-PD-1

Primary human GBM cells

Immune activation

T-cell attraction

Murine GL261 implanted C57BL/6 J mouse

Reinforced antitumor response

Survival benefit

Immune memory development

[186, 187]

Poly (I:C)

T-cell vaccination

GL261

Ag-specific T-cells infiltration

Murine GL261 implanted C57BL/6 J mouse

Immune memory development

[214]

Poly (ICLC)

Anti-PD-1

n/a

n/a

GL261 mouse glioma mode

Reinforced antitumor response

Survival benefit

[137]

TLR3/TLR9

Poly (I:C) + CpG

n/a

Microglia of GL261, U87, LN229

Reduced tumor cell proliferation

Murine GL261 implanted C57BL/6 J mouse

Tumor suppression

[79]

Poly (I:C) + CpG

CD47 blockade

Microglia of GL261, U87, LN229

Reduced tumor cell proliferation

Murine GL261 implanted C57BL/6 J mouse

Reinforced tumor suppression

[79]

TLR4

LPS

n/a

GSCs of patient-derived GBM xenografts

Inhibited non-GSC cell growth

Fresh human GBM cell implanted xenograft

Tumor regression

[90]

LPS

n/a

U87, U118

GSC differentiation

n/a

n/a

[86]

LPS

n/a

n/a

n/a

Murine GL261 implanted C57BL/6 mouse

Not effective

[95]

LPS

n/a

n/a

n/a

Rat RG2 GSCs implanted Fisher 344 rats

Survival benefit

[100]

LPS

n/a

n/a

n/a

Delayed brain tumor GBM cell implanted wild-type and Tlr-4 knockout BALB/c mice

Subcutaneous GBM injection:

complete tumor removal

Intracranial GBM injection:

Wild-type: survival benefit

LPS

n/a

n/a

n/a

Patient-derived GBM cells implanted T lymphocyte-deficient nude mice

Complete tumor regression

[215]

LPS

Fas agonist antibody

U118, U87

Reduced tumor cell proliferation

n/a

n/a

[151]

G100

Tumor-specific T-cells

n/a

n/a

Murine GL261 cells-implanted C57BL/6, OT-I, PMEL, and B6.SJL mice

Complete tumor regression

[153]

TLR7

Aldara

n/a

GL261

Inhibited tumor cell proliferation (TLR7-independent)

Murine GL261-implanted C57BL/6 mouse

Inhibited tumor growth

[102]

TLR7/TLR8

R848

n/a

n/a

n/a

Murine GL261-implanted C57BL/6 mouse

Inhibited tumor growth

Survival benefit

[95]

R848

n/a

n/a

n/a

Rat CNS-1-implanted Lewis rats

Tumor regression

Immune memory development

[69]

R848

Cyclophosphamide

n/a

n/a

Rat CNS-1-implanted Lewis rat

Reinforced tumor regression

Failed to reject secondary tumor challenge

[69]

TLR9

CpG ODN

n/a

GL261

Inhibited cell proliferation (TLR9-independent)

GL261-implanted C57BL/6 mouse

Inhibited tumor growth

[95]

CpG ODN

n/a

GL261

Tumor cell apoptosis

GL261-implanted C57BL/6 mouse

Survival benefit

[171]

CpG ODN

n/a

U87, U251, C6

Elevated invasion of U87 cells

n/a

n/a

[68]

CpG ODN

n/a

n/a

n/a

Rat 9L and RG2-implanted Fisher 344 mice

Tumor remission in > 30% of the animals

[176]

CpG ODN

Radiotherapy

n/a

n/a

Rat 9L and RG2-implanted Fisher 344 mice

Tumor remission in > 60% of the animals

[176]

CpG ODN

Radiotherapy

U87, CHG-5, U251

Autophagy induction

Orthotopic tumor-bearing nude mice

Autophagosome formation

[177]

CpG ODN

Radiotherapy

U87

Inhibited tumor cell proliferation

Human U87-implanted xenograft in nude mice

Tumor regression

[127]

CpG ODN

Cyclophosphamide

n/a

n/a

Murine GL261-implanted C57BL/6NTac mice

Improved immune response

Tumor regression

Immune memory development

[175]

CpG ODN

Glioma vaccine

GL261

Enhanced T-cell function

Murine GL261-implanted C57BL/6 mouse

Tumor regression

Survival benefit

[190]

CpG ODN

Schizophyllan

C6

Tumor cell apoptosis

n/a

n/a

[180]

CpG

SWNT

K-Luc GL261

Inhibited tumor cell migration

n/a

n/a

[179]

Docetaxel

HDL-CpG

Radiation

GL26, CNS-1, HF2303, U251

GBM cell death

Murine GL261-implanted C57BL/6 mouse

Tumor regression

Survival benefit

Immune memory development

[181]