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. 2022 Apr 7;20:44. doi: 10.1186/s12964-022-00854-y

Table 2.

Monotherapy using immune checkpoint inhibitors (ICIs) in preclinical models (animal study)

Tumor Target ICs Main results References
Glioma CTLA-4

Induction of long-term survival in 80% of treated mice

Reduction of CD4+ CD25+ Foxp3+ GITR+ Treg cell density

[69]
Mesothelioma CTLA-4

Inhibition of tumor development at the early stage of tumor development

Improving frequency of CD4 and CD8 T cells infiltrating the tumor

[73]
Hepatocellular carcinoma (HCC) CTLA-4

Simulating longer survival in treated mice than control mice

Amelioration of expression of CD4+ lymphocytes in residual tumors and IFN-γ generation

[74]
NA CTLA-4 Inhibition of CD4+ CD25+ Treg function [17]
Melanoma CTLA-4

Augmentation of intratumoral T effector cell density in TME

Reducing intratumoral Treg density in TME

[258]
Colon adenocarcinoma CTLA-4

Enhancement of intratumoral T effector cell density in TME

Plummeting intratumoral Treg density in TME

[70]
Colon adenocarcinoma CTLA-4 Inspiring anti-tumor response by immune cell [259]
Prostate cancer CTLA-4 Modification of Treg activities is required for the anti-tumor impacts of the CTLA-4 blockade [260]
Sarcomas CTLA-4 Anti-tumor immunotherapy by CTLA-4 blockade depends on the gut microbiota [261]
Melanoma CTLA-4 Loss of IFN-γ axes in tumor cells is contributed to the cell resistance to anti-CTLA-4 therapy [262]
Melanoma CTLA-4 Suppression of melanoma stem cells tumourigenesis [72]
Melanoma PD-1/PD-L1 Tumors tempering the mitochondrial function in T cells show resistance to PD-1 blockade therapy [263]
Oral squamous cell carcinoma (OSCC) PD-1/PD-L1

Provoking the IFNγ, STAT1 activation and the making of the T-cell effector granzyme B in infiltrating cells

Triggering apoptosis in the epithelial cells of the oral lesions

[82]
Pancreatic ductal adenocarcinoma (PDA) PD-1/PD-L1 Mobilization of CD8+ T Cells by CXCR4 inhibition enables PD-1 checkpoint therapy [86]
Myeloma PD-1/PD-L1 Inhibition of tumor cell growth transiently [84]
Melanoma PD-1/PD-L1 Inhibition of tumor cell growth [264]

Programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), cytotoxic-T-lymphocyte-associated protein 4 (CTLA-4), interferon-gamma (IFNγ), signal transducer and activator of transcription (STAT1), Forkhead box P3 (Foxp3), glucocorticoid-induced tumor necrosis factor receptor (GITR), regulatory T cells (Tregs), C-X-C chemokine receptor type 4 (CXCR4)