Table 1 Studies investigating immune cell response and effect on prognosis in epithelial ovarian cancer
Paper | Study | Sample size | Type of immune infiltrate | Conclusion | Effect on prognosis |
|---|---|---|---|---|---|
Woo, E.Y. et al., 2001 [4] | Immunohistochemistry and flow cytometric analysis | 9 | CD4(+)CD25(+) T cells CD8(+)CD25(+) T cells | Increased % of CD4(+)CD25(+) T cells present in ovarian cancer. CD8(+) T cells expressed low levels of CD25 | Not discussed |
Zhang et al., 2003 [5] | Immunohistochemistry | 186 | CD3(+) T cells | The presence of intratumoral T cells correlated with delayed recurrence and an increased expression of IFN γ, IL-2, within the tumor. The absence of intratumoral T cells was associated with increased levels of VEGF. | Increased CD3(+) T cells is associated with increased survival |
Curiel, T.J., et al., 2004 [6] | Immunohistochemistry | 104 | CD4(+)CD25(+)FOXP3(+) T(reg) cells | T(reg) cells suppress tumor-specific T cell immunity and contribute to growth of human tumors in vivo. T(reg) cells are associated with a high death hazard and reduced survival | T(reg) cells are associated with reduced survival |
Sato, E., et al., 2005 [7] | Immunohistochemistry | 117 | CD8(+) T cells CD3(+) T cells CD8(+)/CD4(+) T cell ratio | Increased CD8+ T cells is associated with increased survival No association between CD3+ TILs and survival Increased CD8(+):CD4(+) associated with better survival | Increased CD8+ T cells is associated with increased survival No association between CD3+ TILs and survival Increased CD8(+):CD4(+) associated with increased survival |
Hamanishi, J., et al., 2007 [8] | Immunohistochemistry | 70 | PD-L1 expression on tumour cells CD8(+) T cells | Increased PD-L1 expression on tumour cells is associated with decreased CD8(+) T cells and decreased survival Increased CD8(+) t cells is independently associated with increased survival | Increased CD8(+) t cells is associated with increased survival |
Tomsova et al., 2007 | Immunohistochemistry | 116 | CD3(+) T cells | CD3(+) TILs are associated with increased survival | Increased CD3(+) T cells is associated with increased survival |
Shah, C.A., et al., 2008 [10] | Immunohistochemistry | 119 | CD3(+) T cells CD8(+) T cells CD68(+) TAMs FoxP3(+) Tregs | TIL and TAM levels are positively correlated Patients with greater TILs are more likely to be optimally cytoreduced The presence of circulating tumor DNA does not correlate with TILs, TAMs, or Tregs No association between any cell type and survival seen | No association between any cell type and survival seen |
Adams, S.F., et al., 2009 [11] | Immunohistochemistry | 134 | CD3(+) T cells CD8(+) T cells FoxP3(+) Tregs | Increased CD8(+) T cells is associated with increased survival No difference in survival associated with the other cell types | Increased CD8(+) T cells is associated with increased survival No difference in survival associated with the other cell types |
Clarke, B., et al., 2009 [12] | Immunohistochemistry | 500 | CD8(+) T cells CD3(+) T cells | Increased CD8(+) T cells is associated with increased survival Increased CD3(+) T cells is not associated with any difference in survival On subgroup analysis: For serous ovarian carcinomas, increased CD3(+) and CD8(+) T-cells correlated with improved survival For endometrioid and clear cell carcinomas there is no association between CD3(+) or CD8(+) and survival | Increased CD8(+) T cells is associated with increased survival Increased CD3(+) T cells is not associated with any difference in survival |
Leffers et al., 2009 [13] | Immunohistochemistry | 306 | CD8(+) T cells CD45RO(+) Tmems FoxP3(+) Tregs | increased CD8(+) CTL and CD8(+)/FoxP3(+) ratio is associated with increased survival in advanced stage patients increased CD8(+) T cells and FoxP3(+) Tregs is associated with increased survival | increased CD8(+) CTL and CD8(+)/FoxP3(+) ratio is associated with increased survival in advanced stage patients increased CD8(+) T cells and FoxP3(+) Tregs is associated with increased survival |
Stumpf et al., 2009 [14] | Immunohistochemistry | 100 | CD20(+) B cells CD3(+) T cells CD4(+) T cells CD8(+) T cells | CD3(+) T cells and CD8(+) T cells are associated with increased survival | CD3(+) T cells and CD8(+) T cells are associated with increased survival |
Webb et al., 2014 [15] | Immunohistochemistry | 497 | CD103(+) T cells | CD103(+) TILs comprise intraepithelial, activated CD8(+) T cells, and NK cells and are strongly associated with patient survival in HGSC | CD103(+) TILs are strongly associated with patient survival in HGSC |
Darb-Esfahani et al. 2016 [16] | Immunohistochemistry | 215 | CD3+, PD-1+, and PD-L1+ T cells | CD3+, PD-1+, and PD-L1+ TILs densities were correlated with increased survival Moreover, high PD-1+ TILs as well as PD-L1+ TILs densities added prognostic value to CD3 + TILs | CD3+, PD-1+, and PD-L1+ TILs densities were correlated with increased survival in HGSC |
Woulters et al. 2016 [17] | Immunohistochemistry | 171 | CD8(+) T cells CD27(+) T cells | A prognostic benefit for patients with high intratumoral CD8(+) TIL was observed if primary surgery had resulted in a complete cytoreduction, optimal or incomplete cytoreduction fully abrogated the prognostic effect of CD8(+) TIL. Neither CD8(+) nor CD27(+) cell infiltration was of prognostic benefit in patients treated with neoadjuvant chemotherapy. | CD8+ TILs interact with treatment to affect prognosis |
Bösmüller et al. 2016 [18] | Immunohistochemistry | 135 | CD3 T cells CD103 T cells | Both the presence of CD103 cells, as well as high numbers of intraepithelial CD3 lymphocytes (CD3E), showed a significant correlation with overall survival | Both the presence of CD103 cells, as well as high numbers of intraepithelial CD3 lymphocytes (CD3E), showed a significant correlation with overall survival |
Strickland et al. 2016 [19] | Immunohistochemistry | 245 | CD3+ T cells CD8+ T cells | Increased CD3+ and CD8+ TILs associated with increased survival | Increased CD3+ and CD8+ TILs associated with increased survival |
Kroeger et al. 2016 [20] | immunohistochemistry | CD20+ Tcells CD4+ Tcells CD8+ T cells Plasma cells | CD8(+) TIL carried prognostic benefit only in the presence of PCs and these other TIL subsets. | CD8(+) TIL carried prognostic benefit only in the presence of PCs and these other TIL subsets. |