Table 5.

Potential TILs-related immunotherapy for CCA

Ref	Author	Year	Country	Experimental methods	Tumor type	Treatment	Outcomes
[45]	Diggs L	2020	USA	Animal model	iCCA	Combined anti-CD40/PD-1	Impaired iCCA cell growth, prolonged mice survival.
[46]	Sawasdee N	2020	Thailand	Cell culture experiment	CCA	Gemcitabine combined with cytotoxic T-lymphocytes (CTLs)	Gemcitabine in combination with CTLs promotes cancer cell death.
[47]	Jiraviriyakul A	2019	Thailand	Cell culture experiment	CCA	Honokiol plus dendritic cells (DC)-based vaccine	T lymphocytes stimulated with DCs pulsed with cell lysates of honokiol-treated CCA cells significantly increased specific killing of human CCA cells compared to DCs pulsed with cell lysates of untreated CCA cells.
[48]	Morisaki T	2012	Japan	Cell culture experiment	CCA	Cytokine-activated killer (CAK) cells with cetuximab	Combining CAK cells with cetuximab significantly enhanced cytotoxicity.
[49]	Pan YR	2020	China	Animal model	iCCA	DNA vaccination targeting CTLA4–PD-L1	DNA vaccination targeting CTLA4–PD-L1 triggered the production of specific antibodies and suppressed tumor growth in an iCCA rodent model.
[35]	Fukuda Y	2020	Japan	Animal model	iCCA	CXCL9	CXCL9 knockout leads to greater tumor burden by disrupting natural killer cell recruitment into the tumor in mice

Various studies investigated potential immunotherapy based on tumor infiltrating lymphocytes in animal models or cell experiments

CAK Cytokine-activated killer, CCA cholangiocarcinoma, CTLs cytotoxic T-lymphocytes, CTLA4 cytotoxic T-Lymphocyte associated protein 4, DCs dendritic cells, iCCA intrahepatic cholangiocarcinoma, PD1 programmed cell death protein 1, PD-L1 programmed cell death 1 ligand 1, RFS relapse-free survival