Table 4 The relationship between the number or density of TILs with the prognosis of CCA
From: The role of tumor-infiltrating lymphocytes in cholangiocarcinoma
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). |