Table 3 Molecular pathogenesis of CCA related to TILs
From: The role of tumor-infiltrating lymphocytes in cholangiocarcinoma
Ref | Author | Year | Country | Investigated genes, cytokines or molecular pathways | Sample size | Tumor type | Experimental materials | Experimental methods and assessment of TILS | Main findings |
|---|---|---|---|---|---|---|---|---|---|
[34] | Yoon JG | 2021 | Korea | KRAS and CIN | 121 | iCCA=33, eCCA=35, dCCA=53 | tissue | targeted sequencing, IHC | KARS altered and chromosomal instable tumors are associated with resistance to immunotherapy. |
[33] | Kim HD | 2021 | Korea | Wnt/β-catenin and TGF-β signalling pathways | 33 | iCCA | blood, tissue | flow cytometry, multiplexed IHC, RNA sequencing | Wnt/β-catenin and TGF-β signalling pathways decrease CD69+CD103+ TRM-like CD8+ TILs. |
[35] | Fukuda Y | 2020 | Japan | CXCL9 | 70 | iCCA | tissue | IHC | In iCCA, CXCL9 expression is closely correlated with prolonged postoperative survival and an increased number tumor-infiltrating NK cells. |
[36] | Goeppert B | 2019 | Germany | Microsatellite instability (MSI-H) | 308 | iCCA=159,pCCA=106,dCCA=43 | tissue | TMA, IHC, DNA extraction | MSI-H CCA is associated with a high number of TILs. |
[37] | Cornillet M | 2019 | Sweden | KIR and HLA gene | 148 | CCA | blood | rtPCR, IHC, flow cytometry, RNA, sequencing | HLA and KIR-positive NK cells infiltrate CCA. |
[38] | Thepmalee C | 2018 | Thailand | IL-10 and TGF-b | n. a. | n. a. | cell | cell culture, Western blot, IHC | Inhibition of IL-10 and TGF-b enhances T-cell response against CCA cells. |
[39] | Panya A | 2018 | Thailand | PRKAR1A | n. a. | n. a. | tissue, cell | IHC, DNA sequencing, Western blot, ELISA | Activated T cells are significantly associated with the expression levels of PRKR1A in CCA cells. |
[40] | Qian Y | 2017 | China | aPKC-i/P-Sp1/Snail Signaling | 64 | CCA | tissue, cell | IHC, Cell culture, Western blot, PCR, quantitative real-time flow cytometry | aPKC-i/P-Sp1/Snail signaling may play an important role in recruiting TILs. |
[41] | Junking M | 2017 | Thailand | RNA-pulsed dendritic cells | n. a. | CCA | cell | cell culture, flow cytometry | Pooled mRNA from three CCA cell lines significantly increased the specific killing capacity of activated T lymphocytes. |
[42] | Carnevale G | 2017 | Italy | Fas/FasL pathway | n. a. | iCCA | cell | cell culture, Western blot, IHC, flow cytometry | iCCA cells have immune-modulatory properties by inducing apoptosis of T and NK cells via the Fas/FasL pathway. |
[43] | Duan SG | 2010 | China | MAPK-ERK pathway | n. a. | CCA | cell | cell culture, Western blot, real-time PCR, animal model, RNA isolation and silencing | Laminin-mediated MAPK-ERK pathway induces FasL Expression, subsequently CCA cells kill the Fas-expressing TILs. |
[44] | Ye Y | 2009 | China | B7-H1/PD-1 pathway | 31 | iCCA | tissue | IHC, DNA extraction | B7-H1/PD-1 pathway may be linked to malignant potential of iCCA and contribute to tumor immune evasion by promoting CD8+TILs apoptosis. |