Cervical Cancer: Emerging Immune Landscape and Treatment

Figures & data

Table 1 Differences in Immunophenotype Between Active and Suppressive Cells for Cervical Cancer

	Immune Active Cell	Immune Suppressive Cell
T cell	Th1 secretes anti-tumor factors IL-2, IFN-γ; CTL increases.	Th2 via IL-10, Th17 via IL-17, Tregs via IL-12, IL-21, abundant immunosuppressive cytokines infiltrate.
B cell	Unknown	B cells may promote tumor progression.
NK cell	CD56 NK cells increase IFN- γ, TNF-α.	/
DC	DCs Elicit Th1 and CTL response	/
Macrophage	M1 secretes TNF-α, kills pathogens and promotes Th1 response.	TAM refers to M2, higher immune infiltrates including TGF-ß, VEGF and PD-L1 to elicit tumor promotion and Th2 response.
EOS	/	Increased EOS are regulated by cytokines as IL-3, IL-5 and GM-CSF, correlated with prognosis.
MDSC	/	MDSC and IL-10 attenuate tumor growth and inhibit IL-6.

Notes: In this review, immune cells are divided into immune active and suppressive cells to better demonstrate CC’s immune microenvironment. That is to say, immune active cells tend to fight against cancer development while immune suppressive cells exert pro-inflammatory or cancer progression role.

Table 2 Studies of Immune Checkpoint Inhibitor PD-1/PD-L1 and CTLA4 from Clinicaltrials.gov (Accessed 15th April 2020)

Clinical Trial Identifier	Agent	Immune Target	Primary Endpoint	Sample Size	Status^a	Phase^b
NCT1693783	Ipilimumab	CTLA-4	response rate	n=44	ongoing	2
NCT1711515	Ipilimumab	CTLA-4	Toxicity	n=34	ongoing	1
NCT1975831	Tremelimumab, Durvalumab (MEDI4736)	CTLA-4, PD-L1	Adverse event	n=106 (include other cancers)	ongoing	1
NCT2257528	Nivolumab	PD-1	response rate	n=26	ongoing	2
NCT2725489	Durvalumab VS Vigil	PD-L1	Adverse event	n=13 (include other cancers)	ongoing	2
NCT2914470	Atezoluzumab	PD-L1	Toxicity	n=12 (include other cancers)	ongoing	1
NCT2921269	Atezoluzumab	PD-L1	Response rate	n=22	ongoing	2
NCT3073525	Atezoluzumab VS Vigil	PD-L1	Adverse event	n=25 (include other cancers)	ongoing	2
NCT3104699	AGEN2034	PD-1	Response rate	n=150	ongoing	1, 2
NCT3635567	Pembrolizumab (MK-3475) VS chemotherapy	PD-1	Overall survival	n=600	ongoing	3

Notes: ^aStatus can be divided into recruit, ongoing, terminated, completed. ^bClinical phase can be divided into 1, 2, 3, 4.