Table 4.
The relationship between the number or density of TILs with the prognosis of CCA
| Ref | Author | Year | Country | Sample(n) | Location of TILs | Subtype of TILs | Assessment Of TILs | Criteria for cut-off (Positive/High Expression) | Follow-up (months) | Endpoint | Prognostic significance |
|---|---|---|---|---|---|---|---|---|---|---|---|
| [17] | Asahi Y | 2020 | Japan | iCCA (78) | IT / PT | CD8+ / Foxp3+ | IHC | Mean (cell count, ×400 HPF) | Not reported | OS | Only a high CD8+ count in the PT area are associated with better OS (p=0.0103), other subtypes and locations are not associated with prognosis. |
| [23] | Lu JC | 2019 | China | iCCA (320) | IT / PT | PD1(+)T | IHC | Score>3 (5%–9% of the tissue section) | Not reported | OS / RRS | High PD1(+) T cells in ICC patients with HBV infection are associated with inferior OS (p =0.026) and a higher RRS (p=0.011). |
| [27] | Ueno T | 2018 | Japan | eCCA (117) | IT | CD4+ / CD8+ / Foxp3+ | IHC | Median (cell count, ×400 HPF) | 27 (median) | OS | High numbers of CD4+ TILs are related to better OS (p=0.049). |
| [22] | Kitano Y | 2018 | Japan | eCCA (114) | IT | CD8+ / Foxp3+ | IHC | Mean (cell count, ×400 HPF) | 62.6 (median) | OS | Low CD8 count and high number of Tregs are associated with worse OS (p=0.04, 0.02). |
| [21] | Kim R | 2018 | USA | eCCA (44) | IT | CD8+CD45RO+ | IHC | ≥100 (cell counts, ×400 HPF) | Not reported | OS | Individuals with CD8+CD45RO+ TILs displayed a longer OS (p=0.013). |
| [28] | Vigano L | 2019 | Italy | iCCA (43) | IT | CD3+ / CD8+ / Foxp3+ | IHC | >0.10% (rate of positive cell staining, 400 HPF) | 42 (median) | OS / RFS | CD3+ and CD8+ infiltrate is associated with longer OS (p=0.001, 0.051) and lower RRS (p=0.01, p=0.004), while Foxp3+ infiltrate is associated with shorter OS (p=0.049). |
| [18] | Goeppert B | 2013 | Germany | eCCA (149) iCCA (157) GBCA (69) | IT / PT | CD4+ / CD8+ / Foxp3+ / CD20+ | IHC | median (cell count, ×400 HPF) | Not reported | OS | Patients with intraepithelial tumor-infiltrating CD4+ and CD8+, show a significantly longer OS (p=0.002, p=0.015). Presence of CD20+ and Foxp3+ T lymphocytes also has a positive prognostic impact (p=0.032, p=0.018). |
| [25] | Oshikiri T | 2003 | Japan | eCCA (58) | IT | CD8+ | IHC | >0 (positive cell count, x200 HPF) | Not reported | OS | Intratumoral CD8+T cells are associated with increased OS (p =0.0001). |
| [24] | Miura T | 2017 | Japan | iCCA (115) | IT | CD8+ | IHC | median (cell count, ×400 HPF) | 38 (median) | OS | CD8+T cells in cancer cell nests is not related to OS (p=0.365). |
| [19] | Hasita H | 2010 | Japan | iCCA (55) | IT | Foxp3+ | IHC | median (cell count, ×400 HPF) | 39.7 (mean) | OS / DFS | Count of Foxp3+ is not correlated with DFS and OS (p=0.09, p=0.23). |
| [30] | Xu YP | 2021 | China | iCCA (140) | IT | CD8+ | IHC | Median (cell count, x400 HPF) | 25 (median) | OS / DFS | High count of infiltrating CD8+ cells is related to longer OS and DFS. |
| [26] | Tian L | 2020 | China | iCCA (322) | IT | CD8+ | mIHC | Median (cell count, x400 HPF) | 27 (median) | OS / TTR | Patients with a high density of CD8+ T cells displayed longer OS (p=0.006) and more favorable TTR (p=0.003) |
| [29] | Wu H | 2021 | China | iCCA (50) | IT / TM | CD8+ | IHC | Median (cell count, x200 HPF) | 26.5 (median) | OS / RPF | A higher number of CD8+ cells in the tumor margin is associated with prolonged OS and RFS (p=0.048, p=0.033). |
| [20] | Kim H | 2021 | Korea | CCA (52) | IT / TM | FoxP3-CD4+ | mIHC | Median (cell count, x400 HPF) | Not reported | OS / RFS | A high density of FoxP3-CD4+ cells in the tumor margin is independently associated with favorable DFS and OS (p=0.005, p=0.004). |
Various studies reported oncological outcome with respect to tumor-infiltrating lymphocytes in cholangiocarcinoma
CCA cholangiocarcinoma, DFS disease free survival, eCCA extrahepatic cholangiocarcinoma, FOXP3 forkhead box P3, GBAC gallbladder cancer, HPF high power field, iCCA intrahepatic cholangiocarcinoma, IT intratumoral, PT peritumoral, Ref reference, RFS relapse-free survival, RRS recurrence rate, TIL tumor-infiltrating lymphocytes, TM tumor margin