Tumor immunotherapies by immune checkpoint inhibitors (ICIs); the pros and cons

Naimi, Adel; Mohammed, Rebar N.; Raji, Ahmed; Chupradit, Supat; Yumashev, Alexei Valerievich; Suksatan, Wanich; Shalaby, Mohammed Nader; Thangavelu, Lakshmi; Kamrava, Siavash; Shomali, Navid; Sohrabi, Armin D.; Adili, Ali; Noroozi-Aghideh, Ali; Razeghian, Ehsan

doi:10.1186/s12964-022-00854-y

Cell Communication and Signaling

Table 2 Monotherapy using immune checkpoint inhibitors (ICIs) in preclinical models (animal study)

From: Tumor immunotherapies by immune checkpoint inhibitors (ICIs); the pros and cons

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)

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ISSN: 1478-811X

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