Table 1

Prognostic relevance of T lymphocytes, dendritic cells (DCs), tertiary lymphoid structures (TLSs) and B cells in primary and metastatic ovarian carcinoma

HistologyStageNo of patientsMethodImpactNoteRef.
T lymphocytes
Primary lesion
CD3+ T cellEOC*III, IV174IHC, IFBeneficialHigh density of intratumoral TILs correlated with improved survival40
HGSOCAll199IHCBeneficialHigh density of CD3+ T cells correlated with improved disease outcome3
CD8+ T cellEOCAll270IHCBeneficialHigh density of CD8+ T cells correlated with favorable disease outcome29
EOCAll117IHCBeneficialHigh density of CD8+ T cells correlated with favorable prognosis30
EOCAll500IHCBeneficialHigh density of CD8+ T cells associated with low BRCA1 expression41
EOCAll1815Meta-analysesBeneficialHigh density of CD3+ and CD8+ T cells correlated with improved disease outcome28
EOCAll497IHC, IFBeneficialHigh density of CD103+CD8+ T cells correlated with improved survival33
EOCII, III, IV203IHC, RT-PCRBeneficialHigh density of CD8+ T cells correlated with favorable disease outcome34
EOCAll70IHCBeneficialCD8+ T cells negatively correlated with PD-L1 expression in tumor35
EOCAll199IHCBeneficialHigh density of CD8+ T cells correlated with improved disease outcome3
HGSOC,
EnOC,
OCCC
All135IHCBeneficialHigh density of CD103+CD8+ T cells correlated with improved disease outcome22
EOCAll7377IHCBeneficialHigh density of CD8+ T cells correlated with prolonged OS44
EOCAll210IHCBeneficialHigh density of intratumoral CD8+ CTLs correlated with favorable disease outcome37
HGSOCIII100IHCBeneficialHigh density and clonal selection of TILs correlated with improved disease survival31
HGSOCAll178IHCBeneficialCD8+ T cells were shown to abolish clinically relevant chemoresistance by altering glutathione and cystine metabolism in malignant cells32
HGSOCAll147IHCBeneficialHigh density of CD8+ T cells correlated with improved disease outcome21
HGSOCAll232IHCBeneficialHigh density of CD8+ T cells correlated with improved disease outcome38
HGSOCAll283IHCBeneficialHigh density of CD8+ T cells correlated with favorable prognosis39
HGSOCAll80IFDetrimentalHigh density of PD-1+TIM-3+CD8+ T cells correlated with poor disease outcome45
CD45RO+ T cellEOCAll270IHCBeneficialHigh density of CD45RO+ memory T cells correlated with increased disease specific survival29
EOCAll33IHCBeneficialHigh density of CD45RO+ T cells correlated with higher survival rate42
TREG cellEOCAll270IHCBeneficialHigh density of TREG cells correlated with favorable disease outcome29
EOCAll92IHC, FCDetrimentalHigh density of CD8+ TREG cells, induced by TGFB1, correlated with poor disease outcome66
EOCAll232IHCDetrimentalHigh density of TREG cells associated with advanced stage of disease and suboptimal debulking38
EOCIII,IV26IHC,FCDetrimentalHigh density of ICOS+ TREG cells, dependent on ICOS-L stimulation by pDC, correlated with poor disease outcome17
EOCAll103IFDetrimentalHigh density of TREG cells, inducing the expression of B7-H4 on TAMs, correlated with poor disease outcome56
EOCAll70IFDetrimentalHigh density of TREG cells in tumor and malignant ascites was associated with increased production of CCL22 by cancer cells and TAMs54
EOCAll869Meta-analysesDetrimentalHigh density of TREG cells correlated with poor disease outcome55
EOCAll210IHCDetrimentalHigh density of TREG cells in lymphoid aggregates correlated with reduced survival time37
HGSOCAll199IHCBeneficialHigh density of TREG cells correlated with improved disease outcome3
HGSOC,
MOC,
Other
All99IHC, RT-PCRDetrimentalHigh density of TREG cells correlated with poor OS and PFS53
HGSOC,
MOC,
OCCC
All25FC,RNAseq, CytofDetrimentalHigh density of TREG cells, suppressing CD8+ T cells proliferation, correlated with poor disease outcome62
CD8/TREGEOCAll270IHCBeneficialHigh ratio of CD8+ T cells/TREG cells correlated with improved disease outcome29
EOCAll117IHCBeneficialHigh CD8+ T cells/TREG cells ratio correlated with favorable prognosis30
EOCAll400IHC,IFBeneficialHigh CD8+ T cells/TREG cells ratio correlated with favorable prognosis57
TREG/TH17EOCIII, IV124IFDetrimentalHigh TREG cells/TH17+ cells ratio, derived by TAMs, associated with disease progression and metastasis60
Metastatic lesion
CD8+ T cellEOCIII, IV147IHCBeneficialHigh density of CD8+ CTLs in omental metastasis correlated with improved disease specific survival29
HGSOCIII, IV80IHCNoneHigh density of CD8+ T cells in peritoneal metastasis were not shown to associate with disease outcome20
CD45RO+ cellEOCIII, IV147IHCBeneficialHigh density of CD45RO+T cells in omental metastasis correlated with improved disease specific survival29
HGSOCIII, IV77FCBeneficialHigh density of CD45RA-CCR7-CD8+ T cells in peritoneal ascites correlated with improved RFS43
TREG cellEOCIII, IV147IHCDetrimentalHigh density of TREG cells in omental ascites, mediated by CCL22 produced by cancer cells and TAMs, correlated with poor disease outcome29
CD8/TREGEOCIII, IV147IHCDetrimentalHigh CD8+ T cells/TREG cells ratio in omental metastasis correlated with poor disease specific survival29
DCs
Primary lesion
mDC*EOCAll33IHCBeneficialHigh density of CD1a+ DCs correlated with improved OS42
n.a.n.a.n.a.FC, IHCBeneficalHigh level of CXCL17 correlated with increased density of B7-H4+ DCs and favorable disease outcome74
n.a.n.a.n.a.FC, IHCBeneficialHigh density of CD103+ DCs, as potent stimulators of CTLs, correlated with favorable disease outcome72
HGSOCAll147IHCBeneficalHigh density of mature DC-LAMP+ DCs correlated with increased frequency of CTLs and improved disease outcome21
pDCn.a.All44FCDetrimentalHigh density of CD4+CD123+BDCA2+ pDC correlated with poor disease outcome77
EOCAll60IHC, FCDetrimentalHigh expression of IDO correlated with reduced density of CD8+ T cells, tumor progression and poor disease outcome78
n.a.n.a.n.a.IHC, FCDetrimentalSDF-1 was shown to induce chemotaxis and protection of pDCs from TAM-mediated apoptosis79
EOCIII, IV26IHC, FCDetrimentalHigh density of HLA-DR+CD123+ pDC mediated stimulation of ICOS+ TREG cells associated with poor disease outcome17
Metastatic lesion
mDCHGSOCIII, IV80IHCBeneficialHigh density of mature DC-LAMP+ DCs in peritoneal metastasis correlated with improved disease outcome20
pDCn.a.All44FCDetrimentalHigh density of CD4+CD123+BDCA2+ pDCs in malignant ascites correlated with poor disease outcome77
TLSs and B cells
Primary lesion
B cell*EOCAll135IHCBeneficialHigh density of CD20+ B cells correlated with improved disease outcome36
EOCAll266RNAseqBeneficialHigh BCR segments correlated with improved prognosis82
EOCAll154IHCDetrimentalHigh density of CD138+ plasma cells correlated with poor disease outcome85
HGSOC, EnOCAll224RNAseqBeneficialHigh expression of CD38 correlated with favorable prognosis84
HGSOCAll194IHCBeneficialHigh density of CD27-CD20+ memory B cells correlated with cytolytic immune response and favorable prognosis81
HGSOCAll147IHCBeneficialHigh density of CD20+ B cells correlated with CTLs response and improved RFS and OS21
HGSOCAll199IHCBeneficialHigh density of CD20+ B cells correlated with favorable disease outcome3
HGSOCAll155IHCBeneficialHigh density of CD20-CD38+CD138+CD79a+ plasma cells correlated with CTLs response and improved disease outcome83
TLSHGSOCAll147IHCNoneThe presence of TLSs was not associated with disease outcome21
HGSOCAll155IHCBeneficialTLSs were shown to facilitate the development of antitumor immunity associated with favorable disease outcome83
Metastatic lesion
B cellHGSOCIII, IV80IHCNoneHigh density of CD20+ B cells in peritoneal metastasis was not associated with disease outcome20
HGSOCIII, IV41IHCBeneficialHigh density of memory 20+ B cells in omental metastasis correlated with cytolytic immune response and favorable disease outcome89
  • *Encompassing all EOC histological subtypes.

  • CTL, cytotoxic T lymphocyte; CXCL9, C-X-C motif chemokine ligand 9; EnOC, endometroid ovarian cancer; EOC, epithelial ovarian carcinoma; FC, flow cytometry; HGSOC, high-grade serous ovarian carcinoma; ICOS, inducible T cell costimulator; IDO, indoleamine 2,3-dioxygenase; IF, immunofluorescence; IHC, immunohistochemistry; LAMP, lysosomal-associated membrane protein; mDC, myeloid DC; MOC, mucinous ovarian cancer; n.a., not available; OCCC, clear cell ovarian cancer; OS, overall survival; PD-1, programmed cell death 1; pDC, plasmacytoid DC; PFS, progression-free survival; RFS, relapse-free survival; RNAseq, RNA-sequencing; TAM, tumor-associated macrophage; TGFB1, transforming growth factor beta 1; TIL, tumor-infiltrating lymphocyte; TREG, regulatory T cell.